Urea and thiourea compounds useful for treatment of coccidiosis

ABSTRACT

The present invention relates to novel compounds, pharmaceutical compositions containing the same as well as a method for treatment of parasitic disorders, wherein said compounds are administered. The present compounds are especially well suited for treatment of coccidiosis, particularly in poultry, and they have general formula (I): 
                 
 
where Y is S or O and R is as defined in the specification.

This application is a 371 of PCT(SE00/02091 filed Oct. 27, 2000.

FIELD OF THE INVENTION

The present invention relates to novel compounds, pharmaceuticalcompositions containing the same as well as a method for treatment ofparasitic disorders, wherein said compounds are administered.

BACKGROUND OF THE INVENTION

The coccidia are intracellular protozoan parasites which are prevalentin all domestic animals as well as in man. They are the cause ofcoccidiosis, which is characterized by enteritis. Coccidia of the genusEimeria cause severe intestinal infections in poultry and ruminants(cattle, sheep e.t.c.). In fact, coccidiosis is one of themost-frequently occurring diseases of poultry (see inter alia “PoultryDiseases” by Jordan, F. T. W. and Pattison, M., 4^(th) ed., pp. 261-276,1996, W. B. Saunders Co. Ltd., London, UK). It deserves mentioning thatthe annual costs for anticoccidial medication is about £5 million in theUK only. In poultry, most cases of coccidiosis are caused by protozoabelonging to the genus Eimeria, such as e.g. E. maxima, E. tenella, E.acervulina, E. necatrix, E. hagani, E. praecox, E. mitis and E.brunetti. Other examples of infectious Eimeria protozoa are E.gallopavonis, E. meleagrimitis, E. adenoeides, E. meleagridis, E.dispersa, E. innocua, E. subrotunda, E. truncata, E. anseris, E. bovis,E. zurnii, E. alabamansis, E. auburnensis, E. ashsata, E. parva, E.faurei, E. arloingi, E. debliecki and E. spinosa.

In poultry, e.g. chickens and turkeys, an outbreak of coccidiosis maywith little or no forewarning lead to a serious infection, and unlessthe birds are promptly treated, the result may be a very high mortality.Animals that survive these types of infections are usually of reducedeconomical value, since they become less efficient in converting feed toweight gain, grow much more slowly than normal animals and frequentlyappear listless. A similar disease scenario may also occur upon coccidiainfection of larger animals, e.g. ruminants and pigs, albeit the problemis in general more severe in poultry.

In the treatment of coccidiosis, a recognized problem is the developmentof resistance to known anticoccidial agents. This problem has beenaddressed in numerous publications, such as in Stephen B. et al., Vet.Parasitol., 69(1-2), pp 19-29, 1997. Indeed, there is a strong andongoing demand in the art for both new and improved antiparasiticcompounds, particularly for the treatment of coccidiosis.

As relevant prior art mention can be made of U.S. Pat. No. 5,776,982, EP0 015 110 and U.S. Pat. No. 4,486,439, which disclose compounds usefulfor treatment of coccidiosis. However, none of these documentsspecifically discloses or suggests the compounds of the presentinvention.

DISCLOSURE OF THE INVENTION

There are now provided novel compounds which surprisingly have efficientantiparasitic properties. Furthermore, the present novel compounds areespecially well suited for treatment of coccidiosis (vide infra). Morespecifically, the present invention relates to a compound having thegeneral formula (I):

wherein

-   -   Y is selected from O and S;    -   R is selected from a group of substituents (a)-(c) consisting of    -   (a) NHR₁ and NHR_(2,) wherein R₁ and R₂ are selected from aryl,        optionally having a straight chain, branched or cyclic saturated        or unsaturated alkyl, hydroxy-alkyl or alkylamine substituent        having 1-6 carbon atoms, and at least one of a group of        substituents (d)-(k) consisting of        -   (d) aryl having at least one electron-withdrawing            substituent selected from CN, NO₂, CF₃, SO₃H, OCN, OH, NCO,            COOH, CHO, halogen, carbohydrate unit, CH(OH)A, OA, C(O)OA,            C(O)A, OC(O)A, S(O)₀₋₂A, S(O)₀₋₂NHA, NHC(O)A, NHC(S)A,            NHC(O)NHA, NHC(S)NHA, NHS(O)₀₂A, NHS(O)₀₋₂NHA,            C(O)NH₀₋₂A₀₋₂, C(S)NH₀₋₂A₀₋₂ and C(S)N(SO₂A)₁₋₂H₀₋₁A₀₋₁            -   wherein A is selected from alkyl, alkenyl, cycloalkyl                and aryl, optionally having at least one of said                electron-withdrawing substituents and/or containing at                least one heteroatom selected from N, S and/or O;        -   (e) aralkyl, where at least one of the alkyl and aryl            moieties have at least one electron-withdrawing substituent            as defined in (d);        -   (f) alkyl having at least one electron-withdrawing            substituent as defined in (d);        -   (g) condensed aryl or diphenyl, optionally having at least            one heteroatom selected from N, S and/or O;        -   (h) cycloalkyl or alkylcycloalkyl;        -   (i) heterocycloalkyl or alkylheterocycloalkyl;        -   (j) heteroaryl or heteroaralkyl;        -   (k) C(NH)NH—Y, wherein Y is selected from CN, NO₂, CF₃,            SO₃H, S(O)₀₋₂A, S(O)₀₋₂NHA, N═C-alkyl, N═C-aryl,            N═C-alkenyl, N═C-heteroaryl, N═C-cyclo-alkyl,            N═C-heterocycloalkyl, N═C-alkenylhetero-aryl, carboxyalkyl,            carboxamidealkyl, alkyl-heterocycloalkyl, C(O)NH₀₋₂aryl₀₋₂,            C(S)NH₀₋₂aryl₀₋₂ and cycloalkyl, alkylcycloalkyl or aralkyl            substituted as defined in (e);            -   where the groups (g)-(k) optionally may have at least                one electron-withdrawing substituent as defined in (d)                and/or a straight chain, branched or cyclic saturated or                unsaturated alkyl, hydroxyalkyl or alkylamine                substituent; where the groups (d)-(k) optionally may                have at least one substituent consisting of any one of                the groups (d)-(k);    -   (b) NR₃R₄ and NR₅R₆, wherein R₃-R₅ are independently selected        from a group of substituents (l)-(n) consisting of        -   (l) aryl;        -   (m) aralkyl;        -   (n) straight chain, branched or cyclic saturated or            unsaturated alkyl or hydroxyalkyl having 1-6 carbon atoms;            -   where the groups (g)-(l) optionally may have at least                one electron-withdrawing substituent as defined in (d)                and/or a straight chain, branched or cyclic saturated or                unsaturated alkyl, hydroxyalkyl or alkylamine                substituent; and at least one of the group of                substituents (d)-(k) and SO₂X, where X is selected from                any one of the substituents (d)-(n) and a group of                substituents (O)-(r) consisting of        -   (o) an -arylalkyl-NH₀₋₂Q₀₋₂ radical, where Q is an            electron-withdrawing substituent as defined in (d);        -   (p) an -arylalkyl-NH₀₋₂T₀₋₂radical, where T is any one of            the substituents (d)-(O);        -   (r) an -arylalkyl-NHC(Y)T radical, where T and Y are as            defined above;            -   where the groups (d)-(r) optionally may have at least                one substituent consisting of any one of the groups                (d)-(r);    -   (c) NR₃R₄ as defined in (b), with the proviso that R₄ optionally        may be hydrogen, and a radical having the general formula (II)        -   wherein Z taken together with the nitrogen atom to which it            is attached forms a nitrogen-containing ring structure and            R₇ represents at least one electron-withdrawing substituent            as defined in (d);            -   where said nitrogen-containing ring structure optionally                may have at least one substituent consisting of any one                of the groups (d)-(r) and SO₂X;                tautomers, solvates and radiolabelled derivatives                thereof; and                pharmaceutically acceptable salts thereof.

As examples of pharmaceutically acceptable salts mention can be made ofacid addition salts, e.g. a salt formed by reaction with hydrohalogenacids, such as hydrochloric acid, sulphuric acid, phosphoric acid,nitric acid, aliphatic, alicyclic, aromatic or hetero-cyclic sulphonicor carboxylic acids, such as formic acid, acetic acid, propionic acid,succinic acid, glycolic acid, lactic acid, malic acid, tartaric acid,citric acid, ascorbic acid, maleic acid, hydroxymaleic acid, pyruvicacid, p-hydroxybenzoic acid, embonic acid, methanesulphonic acid,ethanesulphonic acid, hydroxy-ethanesulphonic acid,halogenbensensulphonic acid, toluenesulphonic acid andnaphthalenesulphonic acid.

In preferred embodiments of the present invention, said cycloalkyl isselected from adamantyl, cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, hexahydrocyclopenta[c]-1H-pyrrolyl, bicyclo[2.2.1]heptanyland 1,4-dioxaspiro[4.5]decanyl.

Moreover, said heterocycloalkyl is preferably selected from furanyl,lactonyl, lactamyl, morpholinyl, piperazinyl, piperidinyl, pyranyl,pyrrolidinyl and 4,5-dihydro-1H-imidazolyl.

Said heteroaryl is preferably selected from imidazolyl, pyridinyl,pyrazinyl, pyrimidinyl, pyrrollyl and thiazolyl.

Furthermore, said condensed aryl is preferably selected from acridinyl,anthracenyl, anthraquinonyl, benzothiazolyl, benzoxadiazolyl, indenyl,2,3-dihydro-1H-indenyl, naphthyl, purinyl, pteridinyl, isoquinolinyl,quinolinyl, quinoxalinyl and 1,2,3,4-tetrahydro-1λ⁶-thiochromenyl.

It is preferred that said nitrogen-containing ring structure is selectedfrom acridinyl, benzothiazolyl, benzoxadiazolyl, imidazolyl,4,5-dihydro-1H-imidazolyl, lactamyl, morpholinyl, piperazinyl,piperidinyl, purinyl, pteridinyl, pyrrolidinyl, pyridinyl, pyrazinyl,pyrimidinyl, pyrrollyl, isoquinolinyl, quinolinyl, quinoxalinyl andthiazolyl. Most preferably, said nitrogen-containing ring structure ispiperazinyl.

In a more preferred embodiment of the present invention, R₁ and R₂ arenot identical. In other words, this particular embodiment relates to anasymmetrically substituted urea or thiourea derivative, as is depictedin Table 1 further hereinbelow.

In another preferred embodiment, NR₃R₄ and NR₅R₆ are not identical.

In the most preferred embodiment of the present invention, at least oneof R₁-R₆ is selected from 3-nitrophenyl, 4-nitrophenyl, 4-fluorophenyl,4-cyanophenyl, 4-carboxy-2,6-diiodophenyl, 3,4-dicarboxyphenyl,3,5-dicarboxyphenyl, 3-carboxyphenyl, 1-carboxycyclopentyl,1-carboxycyclopropyl, 3-carboxy-2,4,5-trifluorophenyl,4-carboxy-3-hydroxyphenyl, 3,4,5-trimethoxyphenyl,2-(4-morpholinyl)ethyl, 2-carboxypyrimidinyl, 2-pyrazinyl,6-chloro-2-pyrazinyl, 5-bromo-2-pyridinyl, 6-bromo-2-pyridinyl,5-chloro-2-pyridinyl, 6-chloro-2-pyridinyl, 3-chloro-4-pyridinyl,4,6-dihydroxy-2-pyrimidinyl, 6-nitro-1,3-benzothiazol-2-yl,carboxymethyl, 2,2,2-trifluoro-ethyl, phenylsulfonyl,(4-nitrophenyl)sulfonyl, (4-fluorophenyl) sulfonyl, (trifluoromethyl)sulfonyl, ethylsulfonyl and 2-naphthylsulfonyl.

In the very most preferred embodiment of the present invention, saidcompound is selected from4-[(anilinocarbothioyl)amino]-3,5-diiodobenzoic acid;3,5-diiodo-4-[[(4-nitrophenyl)sulfonyl]({[(4-nitrophenyl)sulfonyl]anilino}carbothioyl)amino]benzoicacid;4-[[(4-fluorophenyl)sulfonyl]({[(4-fluorophenyl)sulfonyl]anilino}carbothioyl)amino]-3,5-diiodobenzoic acid;4-[[(4-fluorophenyl)sulfonyl]({[(4-fluorophenyl)sulfonyl]-4-nitroanilino}carbothioyl)amino]-3,5-diiodobenzoicacid;

-   3,5-diiodo-4-{({4-nitro[(4-nitrophenyl)sulfonyl]anilino}-carbothioyl)[(4-nitrophenyl)sulfonyl]amino}benzoic    acid; 4-{({4-fluoro[(4-nitrophenyl)sulfonyl]anilino}carbo-thioyl)    [(4-nitrophenyl) sulfonyl]amino}-3,5-diiodobenzoic acid;-   N¹, N⁴-bis (4-nitrophenyl)-1,4-piperazinedicarbothioamide; and-   4-nitro-N-{[4-({4-nitro[(4-nitrophenyl)sulfonyl]anilino}-carbothioyl)-1-piperazinyl]carbothioyl}-N-(4-nitrophen-yl)benzenesulfonamide.

Furthermore, the present invention relates to a compound as set forthabove for use as a pharmaceutical.

Accordingly, the present invention also relates to a pharmaceuticalcomposition comprising a compound as set forth above as activeingredient in association with a pharmaceutically acceptable adjuvant,diluent or carrier.

Moreover, the present invention relates to an animal feed, foodconcentrate or drinking water comprising a compound as set forth above.

It should be noted that the composition and animal feed according to thepresent invention may optionally include two or more of the aboveoutlined compounds.

In addition, the present invention relates to the use of a compound asdefined above for the manufacture of a medicament for treatment ofparasitic disorders, particularly coccidiosis and disorders relatedthereto.

The present invention is also concerned with a method for treatment ofparasitic disorders, particularly coccidiosis and disorders relatedthereto, wherein said method comprises administering to an animal,preferably poultry, of a therapeutically effective amount of a compoundas defined above.

Although the present compounds are especially suitable for treatment ofcoccidiodis, it is anticipated that they are also therapeuticallyefficient against the following protozoa, as set forth below asnon-limiting examples:

-   Trypanosoma spp., such as T. cruzi and T. brucei;-   Toxoplasma, such as T. gondii;-   Plasmodium;-   Babesia spp.;-   Theileria spp.;-   Leishmania, such as L. tropica, L. major and L. donavani;-   Entaamoeba histolytica;-   Giardia intestinalis;-   Hexamita meleagridis;-   Trichomonas spp.

The present compounds are also anticipated to be active againstarthropods or helminth parasites, such as flatworms and nematodes.Typical examples of such parasites are disclosed in U.S. Pat. No.5,863,775, the teachings of which are incorporated herein by reference.

The typical dosage of the compounds according to the present inventionvaries within a wide range and will depend on various factors such asthe particular requirement of each receiving individual and the route ofadministration. The dosage is generally within the range of 0.01-1000mg/kg animal feed or body weight.

Typical compounds according to the present invention comprised by thegeneral formula (I) and having Y as defined above and R selected fromsaid group (a), i.e. compounds having the following general formula(III), are depicted in Table 1 hereinbelow.

TABLE 1 (III)

Y R₁ R₂ Denoted S phenyl 6-nitro-1,3- B35 benzothiazol-2-yl O4-nitrophenyl 6-nitro-1,3- B35-3 benzothiazol-2-yl S phenyl3,5-dicarboxyphenyl B37 S 4-nitrophenyl 3,5-dicarboxyphenyl B37-2 S4-nitrophenyl 6-nitro-1,3- B38 benzothiazol-2-yl S phenyl5-nitro-1,3-thiazol-2-yl B40 S phenyl 3,4,5-trimethoxyphenyl B41 Sphenyl 5-methyl-1,3-thiazol-2-yl B47 S phenyl tetrahydro-2-furanylmethylB48 S phenyl 4-carboxy-2,6-diiodophenyl B49 S 4-carboxy-2,6-diiodophenylcarboxymethyl B49-30 S 4-carboxy-2,6-diiodophenyl 2,3-diiodopropylB49-32 S 4-cyanophenyl phenyl B50 S 4-cyanophenyl 4-nitrophenyl B51 S4-cyanophenyl 4-fluorophenyl B55 S phenyl 2-(4-morpholinyl)ethyl B61 S4-nitrophenyl 2-(4-morpholinyl)ethyl B61-2 S phenyl 4-pyridinylmethylB62 S phenyl 2-[(4-nitrophenyl)- B63 sulfonyl]-1,3-thiazol-5-yl S4-nitrophenyl (2S,5R)-3,3-dimethyl-6-yl- B300 7-oxo-4-thia-1-azabicyclo-[3.2.0]heptane-2- carboxylic acid O 4-nitrophenyl 1-carboxycyclopentylB303 O 4-nitrophenyl (4-carboxycyclohexyl)- B305 methyl O 4-nitrophenyl4-carboxycyclohexyl B306 O 4-nitrophenyl 3-carboxyphenyl B307 S4-nitrophenyl 3-carboxyphenyl B308 O 4-nitrophenyl 4-nitro-2-(trifluoro-B311 methyl)phenyl O 4-nitrophenyl 2-nitro-4-(trifluoro- B312methyl)phenyl O 4-nitrophenyl 4-chloro-3-(trifluoro- B315 methyl)phenylO 4-nitrophenyl 3-carboxy-2,4,5- B316 trifluorophenyl S 4-nitrophenyl3-carboxy-2,4,5- B317 trifluorophenyl S 4-nitrophenyl 2,5-dicyano-3,4,6-B318 trifluorophenyl O 4-nitrophenyl 2,5-dicyano-3,4,6- B319trifluorophenyl O 4-nitrophenyl 3-chloro-2,5,6-trifluoro- B3204-pyridinyl O 4-nitrophenyl 2,2,2-trifluoroethyl B321 S 4-nitrophenyl2,2,2-trifluoroethyl B322 O 4-nitrophenyl 4-(trifluoromethyl)- B326phenyl O 4-nitrophenyl 2-benzoyl-4-iodophenyl B329 S 4-nitrophenyl2-benzoyl-4-iodophenyl B330 S 4-nitrophenyl 3-(4-iodophenyl)- B3321,4-dioxo-1,4-dihydro- 2-naphthalenyl O 4-nitrophenyl 3-(4-iodophenyl)-B333 1,4-dioxo-1,4-dihydro- 2-naphthalenyl S 4-nitrophenyl1-carboxy-2-(4- B334 iodophenyl)ethyl O 4-nitrophenyl 1-carboxy-2-(4-B335 iodophenyl)ethyl O 4-nitrophenyl 1-[3,4-dihydroxy-5- B336(hydroxymethyl)- tetrahydro-2-furanyl]-5- iodo-2-oxo-1,2-dihydro-4-pyrimidinyl S 4-nitrophenyl 1-[3,4-dihydroxy-5- B337 (hydroxymethyl)-tetrahydro-2- furanyl]-5-iodo-2- oxo-1,2-dihydro-4- pyrimidinyl S4-nitrophenyl 1-carboxy-2-[3,5- B340 diiodo-4-(4-hydroxy-3-iodophenoxy)- phenyl]ethyl O 4-nitrophenyl 1-carboxy-2-[3,5-B341 diiodo-4-(4- hydroxy-3-iodophenoxy)- phenyl]ethyl O 4-nitrophenyl1-carboxy-2-(4- B342 hydroxy-3-iodophenyl)- ethyl S 4-nitrophenyl1-carboxy-2-(4- B343 hydroxy-3-iodophenyl)- ethyl O 4-nitrophenyl2-carboxy-4-iodophenyl B344 O 4-nitrophenyl 9-[3,4-dihydroxy-5- B345(iodomethyl)tetra- hydro-2-furanyl]- 9H-purin-6-yl S 4-nitrophenyl9-[3,4-dihydroxy-5- B346 (iodomethyl)tetra- hydro-2-furanyl]-9H-purin-6-yl O 4-nitrophenyl 2-carboxy-3,5,6- B347trichloro-4-pyridinyl O 4-nitrophenyl 2-carboxy-3-quinoxalinyl B348 O4-nitrophenyl 2-carboxy-4-quinolinyl B349 S 4-nitrophenyl2-carboxy-4-quinolinyl B350 S 4-nitrophenyl 2-carboxy-pyrimidinyl B351 S4-nitrophenyl 3-yl-bicyclo-[2.2.1]heptane- B352 2-carboxylic acid S4-nitrophenyl (4-carboxycyclohexyl)- B354 methyl S 4-nitrophenyl3-carboxy-5- B356 hydroxypyrimidinyl S 4-nitrophenyl 3-carboxy-4- B357chloropyrimidinyl O 4-nitrophenyl 2-carboxy-9,10- B358dioxo-9,10-dihydro- 1-anthracenyl O 4-nitrophenyl 3-carboxyadamantylB359 O 4-nitrophenyl (1S,3R)-1-yl-1,3- B361 cyclopentane- dicarboxylicacid O 4-nitrophenyl 2-carboxy-5-ethyl- B362 thiopyrimidinyl O4-nitrophenyl 1,3,3-tricarboxypropyl B363 O 4-nitrophenyl2-carboxypyrazinyl B364 O 4-nitrophenyl 1-carboxycyclopropyl B368 S4-nitrophenyl 1-carboxycyclopropyl B369 O 4-nitrophenyl2-[2,3,4-trihydroxy- B601 1-(1-yl-2-oxoethyl)- butoxy]propanoic acid O4-nitrophenyl 4-oxo-6-[(1R,2S)- B602 1,2,3-trihydroxy-propyl]-4,8-dihydro- 2-pteridinyl O 4-nitrophenyl2,4,5-trihydroxyphenethyl B604 O 4-nitrophenyl 4-carboxy-2,6-dioxo- B6061,2,3,6-tetrahydro-5- pyrimidinyl O 4-nitrophenyl 1,3-dihydroxy-9,10-B607 dioxo-9,10-dihydro- 2-sulfoxy-4-anthracenyl O 4-nitrophenyl1-carboxy-2-(2,4,5- B608 trihydroxyphenyl)ethyl O 4-nitrophenyl1-[3,4-dihydroxy-5- B609 (hydroxymethyl)- tetrahydro-2-furanyl]-6-oxo-1,6-dihydro-4- pyrimidinyl O 4-nitrophenyl (1R,2S)-2-(3,4- B610dihydroxyphenyl)- 2-hydroxy-1-methylethyl O 4-nitrophenyl3,4-dihydroxybenzyl B611 O 4-nitrophenyl 1-[3,4-dihydroxy-5- B612(hydroxymethyl)- tetrahydro-2- furanyl]-5-methyl- 2-oxo-1,2-dihydro-4-pyrimidinyl O 4-nitrophenyl 1-[3,4-dihydroxy-5- B613(hydroxymethyl)tetrahydro- 2-furanyl]-2-thioxo-1,2-dihydro-4-pyrimidinyl O 4-nitrophenyl 1-[3,4-dihydroxy-5- B614(hydroxymethyl)tetrahydro- 2-furanyl]-2-oxo-1,2- dihydro-4-pyrimidinyl O4-nitrophenyl 4,5-dihydroxy-7- B615 {[(4-nitroanilino)-carbonyl]amino}-9,10- dioxo-9,10-dihydro-2- anthracenyl O 4-nitrophenyl3,4-dihydroxyphenethyl B616 O 4-nitrophenyl 2-(3,4-dihydroxyphenyl)-B617 2-hydroxyethyl O 4-nitrophenyl 1,3-dicarboxycyclobutyl B619 O4-nitrophenyl (1R,3R)-1-yl-1,3- B620 cyclopentane- dicarboxylic acid O4-nitrophenyl 2-(2-carboxybenzoyl)- B621 phenyl O 4-nitrophenyl5-carboxy-2-pyridinyl B622 O 4-nitrophenyl 1-carboxycyclohexyl B623 O4-nitrophenyl 2-yl-bicyclo- B624 [2.2.1]heptane-2- carboxylic acid O4-nitrophenyl 2-{[(3-nitro- B635 anilino)carbonyl]- amino}ethyl S4-nitrophenyl 2-{[(3-nitroanilino)- B636 carbothioyl]amino}ethyl O4-nitrophenyl 4-{[(3-nitroanilino)- B637 carbonyl}amino)butyl S4-nitrophenyl 4-{[(3-nitroanilino)- B638 carbothioyl]amino}butyl O4-nitrophenyl 4-{[(4-nitroanilino)- B639 carbonyl]amino}phenyl S4-nitrophenyl 4-{[(4-nitroanilino)- B640 carbothioyl]amino}phenyl O4-nitrophenyl 5-{[(3-nitroanilino)- B641 carbonyl]amino}pentyl S4-nitrophenyl 5-{[(3-nitroanilino)- B642 carbothioyl]amino}pentyl O4-nitrophenyl 4′-{[(4-nitroanilino)- B643 carbonyl]amino}-1,1′-biphen-4-yl S 4-nitrophenyl 4′-{[(4-nitroanilino)- B644carbothioyl]amino}-1,1′- biphen-4-yl O 4-nitrophenyl 4,6-dihydroxy-2-B645 pyrimidinyl S 4-nitrophenyl 4,6-dihydroxy-2- B646 pyrimidinyl O4-nitrophenyl 3,3′-dichloro-4′- B647 {[(4-nitroanilino)-carbonyl]amino}- 1,1′-biphen-4-yl S 4-nitrophenyl 3,3′-dichloro-4′- B648{[(4-nitroanilino)- carbothioyl]amino}- 1,1′-biphen-4-yl O 4-nitrophenyl3,3′-dimethyl-4′- B649 {[(4-nitroanilino)- carbonyl]amino}-1,1′-biphen-4-yl S 4-nitrophenyl 3,3′-dimethyl-4′- B650{[(4-nitroanilino)- carbothioyl]amino}- 1,1′-biphen-4-yl O 4-nitrophenyl(4-diethylamino-1- B651 methyl)butyl S 4-nitrophenyl (4-diethylamino-1-B652 methyl)butyl O 4-nitrophenyl 6-{[(4-nitroanilino)- B653carbonyl]-amino}-3- acridinyl S 4-nitrophenyl 6-{[(4-nitroanilino)- B654carbothioyl]- amino}-3-acridinyl O 4-nitrophenyl 2,4-dibromo-6- B655{[cyclohexyl(methyl)- amino]-methyl}phenyl S 4-nitrophenyl2,4-dibromo-6- B656 {[cyclohexyl(methyl)- amino]methyl}phenyl O4-nitrophenyl 4-(dimethylamino)phenyl B657 S 4-nitrophenyl4-(dimethylamino)phenyl B658 O 4-nitrophenyl 6-chloro-2-pyrazinyl B659 S4-nitrophenyl 6-chloro-2-pyrazinyl B660 O 4-nitrophenyl5-chloro-2-pyridinyl B661 S 4-nitrophenyl 5-chloro-2-pyridinyl B662 O4-fluorophenyl {2-[(E)-(2,6- B663 dichlorophenyl)-methylidene]hydrazino}- (imino)methyl S 4-fluorophenyl {2-[(E)-(2,6-B664 dichlorophenyl)- methylidene]hydrazino}- (imino)methyl O4-fluorophenyl N-(1-acetyl)- B665 imidoformamidyl S 4-fluorophenylN-(1-acetyl)- B666 imidoformamidyl O 4-fluorophenyl N-(2,3-dihydro-1,4-B667 benzodioxin-2-yl-methyl)- imidoformamidyl S 4-fluorophenylN-(2,3-dihydro-1,4- B668 benzodioxin-2-yl-methyl)- imidoformamidyl O4-fluorophenyl N-(3-methyl-2-butenyl)- B669 imidoformamidyl S4-fluorophenyl N-(3-methyl-2-butenyl)- B670 imidoformamidyl O4-fluorophenyl N-(1,4-dioxaspiro- B671 (4.5)dec-2-ylmethyl)-imidoformamidyl S 4-fluorophenyl N-(1,4-dioxaspiro- B672(4.5)dec-2-ylmethyl)- imidoformamidyl O 4-fluorophenylN-(1-(2,6-dichlorophenyl)- B673 2-oxo-ethyl)imido- formamidyl S4-fluorophenyl N-(1-(2,6-dichlorophenyl)- B674 2-oxo-ethyl)imido-formamidyl S 4-fluorophenyl N-cyanoimido- B676 formamidyl O4-fluorophenyl {[(4-fluoroanilino)- B677 carbonyl]amino}- (imino)methylS 4-fluorophenyl {[(4-fluoroanilino)- B678 carbothioyl]amino}-(imino)methyl O 4-fluorophenyl N-{2,3,4,6-tetra- B679hydroxy-5-((iminomethyl)- amino)cyclohexyl}- imidoformamidyl S4-fluorophenyl N-{2,3,4,6-tetra- B680 hydroxy-5-((iminomethyl)-amino)cyclohexyl}- imidoformamidyl O 4-fluorophenylimino(2-{(E)-3-(5-nitro- B681 2-furyl)-1-[(E)-2-(5-nitro-2-furyl)ethenyl]-2- propenylidene}- hydrazino)methyl S 4-fluorophenylimino(2-{(E)-3-(5-nitro- B682 2-furyl)-1-[(E)-2-(5-nitro-2-furyl)ethenyl]-2- propenylidene}- hydrazino)methyl

Compound data and systematic names for the compounds presented in Table1 are as follows:

-   B35 (C₁₄H₁₀N₄O₂S₂; Molecular weight (MW)=330.387):-   N-(6-nitro-1,3-benzothiazol-2-yl)-N′-phenylthiourea;-   B35-3 (C₁₄H₉N₅S; MW=359.318):-   N-(6-nitro-1,3-benzothiazol-2-yl)-N′-(4-nitrophenyl)urea;-   B37 (C₁₅H₁₂N₂O₄S; MW=316.333):-   5-[(anilinocarbothioyl)amino]isophtalic acid;-   B37-2 (C₁₅H₁₁N₃O₆S; MW=361.330):-   5-{[(4-nitroanilino)carbothioyl]amino}isophtalic acid;-   B38 (C₁₄H₉N₅O₄S₂; MW=375.385):-   N-(6-nitro-1,3-benzothiazol-2-yl)-N′-(4-nitrophenyl)-thiourea;-   B39 (C₁₄H₉FN₄O₂S₂; MW=348.377):-   N-(4-fluorophenyl)-N′-(6-nitro-1,3-benzothiazol-2-yl)thiourea;-   B40 (C₁₀H₈N₄O₂S₂; MW=280.328):-   N-(5-nitro-1,3-thiazol-2-yl)-N′-phenylthiourea;-   B41 (C₁₆H₁₈N₂O₃S; MW=318.392):-   N-phenyl-N′-(3,4,5-trimethoxyphenyl)thiourea;-   B47 (C₁₁H₁₁N₃S₂; MW=249.357):-   N-(5-methyl-1,3-thiazol-2-yl)-N′-phenylthiourea;-   B48 (C₁₂H₁₆N₂OS; MW=236.334):-   N-phenyl-N′-(tetrahydro-2-furanylmethyl)thiourea;-   B49 (C₁₄H₁₀I₂N₂O₂S; MW=524.116):-   4-[(anilinocarbothioyl)amino]-3,5-diiodobenzoic acid;-   B49-30 (C₁₀H₈I₂N₂O₄S; MW=506.057):-   4-({[(carboxymethyl)amino]carbothioyl}amino)-3,5-diiodobenzoic acid;-   B49-32 (C₁₁H₁₀I₄N₂O₂S; MW=741.893):-   4-({[(2,3-diiodopropyl)amino]carbothioyl}amino)-3,5-diiodobenzoic    acid;-   B50 (C₁₄H₁₁N₃S; MW=253.323):-   N-(4-cyanophenyl)-N′-phenylthiourea;-   B51 (C₁₄H₁₀N₄O₂S; MW=298.321):-   N-(4-cyanophenyl)-N′-(4-nitrophenyl) thiourea;-   B55 (C₁₄H₁₀FN₃S; MW=271.314):-   N-(4-cyanophenyl)-N′-(4-fluorophenyl)thiourea;-   B61 (C₁₃H₁₉N₃OS; MW=265.376):-   N-[2-(4-morpholinyl)ethyl]-N′-phenylthiourea;-   B61-2 (C₁₃H₁₈N₄O₃S; MW=310.373):-   N-[2-(4-morpholinyl)ethyl]-N′-(4-nitrophenyl) thiourea;-   B62 (C₁₃H₁₃N₃S; MW=243.329)-   N-phenyl-N′-(4-pyridinylmethyl)thiourea;-   B63 (C₁₆H₁₂N₄O₄S₃; MW=420.489):-   N-{2-[(4-nitrophenyl)sulfonyl]-1,3-thiazol-5-yl}-N′-phenylthiourea;-   B300 (C₁₅H₁₆N₄O₅S₂; MW=396.444):-   (2S,5R)-3,3-dimethyl-6-{[(4-nitroanilino)carbothioyl]amino}-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic    acid;-   B303 (C₁₃H₁₅N₃O₅; MW=293.275):-   1-{[(4-nitroanilino)carbonyl]amino}cyclopentanecarboxylic acid;-   B305 (C₁₅H₁₉N₃O₅; MW=321.329):-   4-({[(4-nitroanilino)carbonyl]amino}methyl)cyclohexane-carboxylic    acid;-   B306 (C₁₄H₁₇N₃O₅; MW=307.302)-   4-{[(4-nitroanilino)carbonyl]amino}cyclohexanecarboxylic acid;-   B307 (C₁₄H₁₁N₃O₅; MW=301.254)-   3-{[(4-nitroanilino)carbonyl]amino}benzoic acid;-   B308 (C₁₄H₁₁N₃O₄S; MW=317.321):-   3-{[(4-nitroanilino)carbothioyl]amino}benzoic acid;-   B311 (C₁₄H₉F₃N₄O₅; MW=370.240):-   N-(4-nitrophenyl)-N′-[4-nitro-2-(trifluoromethyl)phenyl]-urea;-   B312 (C₁₄H₉F₃N₄O₅; MW=370.240):-   N-(4-nitrophenyl)-N′-[2-nitro-4-(trifluoromethyl)phenyl]-urea;-   B315 (C₁₄H₁₉ClF₃N₃O₃; MW=359.688):-   N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-(nitrophenyl)-urea;-   B316 (C₁₄H₈F₃N₃O₅; MW=355.226):    2,3,6-trifluoro-5-{[(4-nitroanilino)carbonyl]amino}-benzoic acid;-   B317 (C₁₄H₈F₃N₃O₄S; MW=371.292):-   2,3,6-trifluoro-5-{[(4-nitroanilino)carbothioyl]amino}-benzoic acid;-   B318 (C₁₅H₆F₃N₅O₂S; MW=377.302):-   N-(2,5-dicyano-3,4,6-trifluorophenyl)-N′-(4-nitrophenyl)-thiourea;-   B319 (C₁₅H₆F₃N₅O₃; MW=361.235):-   N-(2,5-dicyano-3,4,6-trifluorophenyl)-N′-(4-nitrophenyl)-urea;-   B320 (C₁₂H₆ClF₃N₄O₃; MW=346.649):-   N-(3-chloro-2,5,6-trifluoro-4-pyridinyl)-N′-(4-nitro-phenyl)urea;-   B321 (C₉H₈F₃N₃O₃; MW=263.173):-   N-(4-nitrophenyl)-N′-(2,2,2-trifluoroethyl)urea;-   B322 (C₉H₈F₃N₃O₂S; MW=279.240):-   N-(4-nitrophenyl)-N′-(2,2,2-trifluoroethyl)thiourea;-   B326 (C₁₄H₁₀F₃N₃O₃; MW=325.243):-   N-(4-nitrophenyl)-N′-[4-(trifluoromethyl)phenyl]urea;-   B329 (C₂₀H₁₄IN₃O₄; MW=487.247):-   N-(2-benzoyl-4-iodophenyl)-N′-(4-nitrophenyl)urea;-   B330 (C₂₀H_(l4)IN₃O₃S; MW=503.314):-   N-(2-benzoyl-4-iodophenyl)-N′-(4-nitrophenyl)thiourea;-   B332 (C₂₃H₁₄IN₃O₄S; MW=555.346):-   N-[3-(4-iodophenyl)-1,4-dioxo-1,4-dihydro-2-naphthalen-yl]N′-(4-nitrophenyl)thiourea;-   B333 (C₂₃H₁₄IN₃O₅; MW=539.279):-   N-[3-(4-iodophenyl)-1,4-dioxo-1,4-dihydro-2-naphthalen-yl]-N′-(4-nitrophenyl)urea;-   B334 (C₁₆H₁₄IN₃O₄S; MW=471.271):-   4-iodo-N-[(4-nitroanilino)carbothioyl]phenylalanine;-   B335 (C₁₆H₁₄IN₃O₅; MW=455.204):-   4-iodo-N-[(4-nitroanilino)carbonyl]phenylalanine;-   B336 (C₁₆H₁₆IN₅O₈; MW=533.232):-   N-{1-[3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-iodo-2-oxo-1,2-dihydro-4-pyrimidinyl}-N′-(4-nitrophenyl)urea;-   B337 (C₁₆H₁₆IN₅O₇S; MW=549.298):-   N-{1-[3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-iodo-2-oxo-1,2-dihydro-4-pyrimidinyl}-N′-(4-nitrophenyl)thiourea;-   B340 (C₂₂H₁₆I₃N₃O₆S; MW=831.158):-   4-(4-hydroxy-3-iodophenoxy)-3,5-diiodo-N-[(4-nitroanilino)carbothioyl]phenylalanine;-   B341 (C₂₂H₁₆I₃N₃O₇; MW=815.092):-   4-(4-hydroxy-3-iodophenoxy)-3,5-diiodo-N-[(4-nitroanilino)carbonyl]phenylalanine;-   B342 (C₁₆H₁₄IN₃O₆; MW=471.203):-   4-hydroxy-3-iodo-N-[(4-nitroanilino)carbonyl]phenyl-alanine;-   B343 (C₁₆H₁₄IN₃O₅S; MW=487.270):-   3-(4-hydroxy-3-iodophenyl)-2-{[(4-nitroanilino)carbonyl]-amino}propanethioic    O-acid;-   B344 (C₁₄H₁₀IN₃O₅; MW=427.151):-   5-iodo-2-{[(4-nitroanilino)carbonyl]amino}benzoic acid;-   B345 (C₁₇H₁₆IN₇O₆; MW=541.257):-   N-{9-[3,4-dihydroxy-5-(iodomethyl)tetrahydro-2-furanyl]-9H-purin-6-yl}-N′-(4-nitrophenyl)urea;-   B346 (C₁₇H₁₆IN₇O₅S; MW=557.324):-   N-{9-[3,4-dihydroxy-5-(iodomethyl)tetrahydro-2-furanyl]-9H-purin-6-yl}-N′-(4-nitrophenyl)thiourea;-   B347 (C₁₃H₇Cl₃N₄O₅; MW=405.577):-   3,5,6-trichloro-4-{[(4-nitroanilino)carbonyl]amino}-2-pyridinecarboxylic    acid;-   B348 (C₁₆H₁₁N₅O₅; MW=353.289):-   3-{[(4-nitroanilino)carbonyl]amino}-2-quinoxalinecarboxylic acid;-   B349 (C₁₇H₁₂N₄O₅; MW=352.301):-   4-{[(4-nitroanilino)carbonyl]amino}-2-quinoline-carboxylic acid;-   B350 (C₁₁H₁₂N₄O₄S; MW=368.368):-   4-{[(4-nitroanilino)carbothioyl]amino}-2-quinoline-carboxylic acid;-   B351 (C₁₂H₉N₅O₄S; MW=319.297):-   4-{[(4-nitroanilino)carbothioyl]amino}-5-pyrimidine-carboxylic acid;-   B352 (C₁₅H₁₇N₃O₄S; MW=335.379):-   3-{[(4-nitroanilino)carbothioyl]amino}bicyclo[2.2.1]-heptane-2-carboxylic    acid;-   B354 (C₁₅H₁₉N₃O₄S; MW=337.395):-   4-({[(4-nitroanilino)carbothioyl]amino}methyl)cyclo-hexanecarboxylic    acid;-   B356 (C₁₂H₉N₅O₅S; MW=335.297):-   6-hydroxy-2-{[(4-nitroanilino)carbothioyl]amino}-4-pyrimidinecarboxylic    acid;-   B357 (C₁₂H₈ClN₅O₄S; MW=353.742):-   5-chloro-2-{[(4-nitroanilino)carbothioyl]amino}-4-pyrimidinecarboxylic    acid;-   B358 (C₂₂H₁₃N₃O₇; MW=431.355):-   1-{[(4-nitroanilino)carbonyl]amino}-9,10-dioxo-9,10-dihydro-2-anthracenecarboxylic    acid;-   B359 (C₁₈H₂₁N₃O₇; MW=359.377):-   3-{[(4-nitroanilino)carbonyl]amino}-1-adamantane-carboxylic acid;-   B361 (C₁₄H₁₅N₃O₇S; MW=337.285):-   (1S,3R)-1-{[(4-nitroanilino)carbonyl]amino}-1,3-cyclo-pentanedicarboxylic    acid;-   B362 (C₁₄H₁₃N₅O₅S; MW=363.350):-   2-(ethylsulfanyl)-4-{[(4-nitroanilino)carbonyl]amino}-5-pyrimidinecarboxylic    acid;-   B363 (C₁₃H₁₃N₃O₉; MW=355.257):-   3-{[(4-nitroanilino)carbonyl]amino}-1,1,3-propanetricarboxylic acid;-   B364 (C₁₂H₉N₅O₅; MW=303.231):-   3-{[(4-nitroanilino) carbonyl]amino}-2-pyrazinecarboxylic acid;-   B368 (C₁₁H₁₁N₃O₅; MW=265.222):-   1-{[(4-nitroanilino)carbonyl]amino}cyclopropanecarboxylic acid;-   B369 (C₁₁H₁₁N₃O₄S; MW=281.289):-   1-{[(4-nitroanilino)carbothioyl]amino}cyclopropanecarboxylic acid;-   B601 (C₁₆H₂₁N₃O₁₀; MW=415.352):-   2-[2,3,4-trihydroxy-1-(1-{[(4-nitroanilino)carbonyl]-amino)-2-oxoethyl)butoxy]propanoic    acid;-   B602 (C₁₆H₁₅N₇O₇; MW=417.333):-   N-(4-nitrophenyl)-N′-{4-oxo-6-[(1R,2S)-1,2,3-trihydroxy-propyl]-4,8-dihydro-2-pteridinyl}urea;-   B604 (C₁₅H₁₅N₃O₆; MW=333.296):-   N-(4-nitrophenyl)-N′-(2,4,5-trihydroxyphenethyl)urea;-   B606 (C₁₂H₉N₅O₇; MW=335.229):-   5-{[(4-nitroanilino)carbonyl]amino}-2,6-dioxo-1,2,3,6-tetrahydro-4-pyrimidinecarboxylic    acid;-   B607 (C₂₁H₁₃N₃O₁₀S; MW=499.408):-   1,3-dihydroxy-4-{[(4-nitroanilino)carbonyl]amino)-9,10-dioxo-9,10-dihydro-2-anthracenesulfonic    acid;-   B608 (C₁₆H₁₅N₃O₈; MW=377.306):-   2,4,5-trihydroxy-N-[(4-nitroanilino)carbonyl]phenyl-alanine;-   B609 (C₁₆H₁₇N₅O₈; MW=407.335):-   N-{1-[3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-6-oxo-1,6-dihydro-4-pyrimidinyl}-N′-(4-nitro-phenyl)urea;-   B610 (C₁₆H₁₇N₃O₆; MW=347.323):-   N-[(1R,2S)-2-(3,4-dihydroxyphenyl)-2-hydroxy-1-methylethyl]-N′-(4-nitrophenyl)urea;-   B611 (C₁₄H₁₃N₃O₅; MW=303.270):-   N-(3,4-dihydroxybenzyl)-N′-(4-nitrophenyl) urea;-   B612 (C₁₇H₁₉N₅O₈; MW=421.362):-   N-}1-[3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-methyl-2-oxo-1,2-dihydro-4-pyrimidinyl}-N′-(4-nitrophenyl)urea;-   B613 (C₁₆H₁₇N₅O₇S; MW=423.402):-   N-{1-[3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2-thioxo-1,2-dihydro-4-pyrimidinyl}-N′-(4-nitrophenyl)urea;-   B614 (C₁₆H₁₇N₅O₈; MW=407.335):-   N-{1-[3,4-dihydroxy-S-(hydroxymethyl)tetrahydro-2-furanyl]-2-oxo-1,2-dihydro-4-pyrimidinyl}-N′-(4-nitrophenyl)urea;-   B615 (C₂₈H₁₈N₆O₁₀; MW=598.477):-   N-(4,5-dihydroxy-7-{[(4-nitroanilino)carbonyl]amino}-9,10-dioxo-9,10-dihydro-2-anthracenyl)-N′-(4-nitrophen-yl)urea;-   B616 (C₁₅H₁₅N₃O₅; MW=317.297):-   N-(3,4-dihydroxyphenethyl)-N′-(4-nitrophenyl)urea;-   B617 (C₁₅H₁₅N₃O₆; MW=333.296):-   N-[2-(3,4-dihydroxyphenyl)-2-hydroxyethyl]-N′-(4-nitrophenyl)urea;-   B619 (C₁₃H₁₃N₃O₇; MW=323.258):-   1-{[(4-nitroanilino)carbonyl]amino}-1,3-cyclobutane-dicarboxylic    acid;-   B620 (C₁₄H₁₅N₃O₇; MW=337.285):-   (1R,    3R)-1-{[(4-nitroanilino)carbonyl]amino}-1,3-cyclopentanedicarboxylic    acid;-   B621 (C₂₁H₁₅N₃O₆; MW=405.360):-   2-(2-{[(4-nitroanilino)carbonyl]amino}benzoyl)benzoic acid;-   B622 (C₁₃H₁₀N₄O₅; MW-302.242):-   6-{[(4-nitroanilino)carbonyl]amino}nicotinic acid;-   B623 (C₁₄H₁₇N₃O₅; MW=307.302):-   1-{[(4-nitroanilino)carbonyl]amino}cyclohexanecarboxylic acid;-   B624 (C₁₅H₁₇N₃O₅; MW=319.313):-   2-{[(4-nitroanilino)carbonyl]amino}-bicyclo[2.2.1]-heptane-2-carboxylic    acid;-   B635 (C₁₆H₁₆N₆O₆; MW=388.335):-   N′-(2-{[(3-nitroanilino)carbonyl]amino}ethyl)-N-(4-nitrophenyl)urea;-   B636 (C₁₆H₁₆N₆O₄S₂; MW=420.468):-   N′-(2-{[(3-nitroanilino)carbothioyl]amino}ethyl)-N-(4-nitrophenyl)thiourea;-   B637 (C₁₈H₂₀N₆O₆; MW=416.388):-   N′-(4-{[(3—nitroanilino)carbonyl]amino}butyl)-N-(4-nitrophenyl)urea;-   B638 (C₁₈H₂₀N₆O₄S₂; MW=448.521):-   N′-(4-{[(3-nitroanilino)carbothioyl]amino}butyl)-N-(4-nitrophenyl)thiourea;-   B639 (C₂₀H₁₆N₆O₆; MW=436.378):-   N′-(4-{[(4-nitroanilino)carbonyl]amino}phenyl)-N-(4-nitrophenyl)urea;-   B640 (C₂₀H₁₆N₆O₄S₂; MW=468.511):-   N′-(4-{[(4-nitroanilino)carbothioyl]amino}phenyl)-N-(4-nitrophenyl)thiourea;-   B641 (C₁₉H₂₂N₆O₆: MW=430.415):-   N′-(5-{[(3-nitroanilino)carbonyl]amino}pentyl)-N-(4-nitrophenyl)urea;-   B642 (C₁₉H₂₂N₆O₄S₂; MW=462.548):-   N′-(5-{[(3-nitroanilino)carbothioyl]amino}pentyl)-N-(4-nitrophenyl)thiourea;-   B643 (C₂₆H₂₀N₆O₆; MW=512.474):-   4,4′-bis{[(4-nitroanilino)carbonyl]amino}-1,1′-biphenyl;-   B644 (C₂₆H₂₀N₆O₄S₂; MW=544.607):-   4,4′-bis{[(4-nitroanilino)carbothioyl]amino}-1,1′-biphenyl;-   B645 (C₁₁H₉N₅O₅; MW=291.220):-   N-(4,5-dihydroxy-2-pyrimidinyl)-N′-(4-nitrophenyl)urea;-   B646 (C₁₁H₉N₅O₄S; MW=307.286):-   N-(4,5-dihydroxy-2-pyrimidinyl)-N′-(4-nitrophenyl)-thiourea;-   B647 (C₂₆H₁₈Cl₂N₆O₆; MW=581.363):-   3,3′-dichloro-4,4′-bis{[(4-nitroanilino)carbonyl]amino}-1,1′-biphenyl;-   B648 (C₂₆H₁₈Cl₂N₆O₄S₂; MW=613.497):-   3,3′-dichloro-4,4′-bis{[(4-nitroanilino)carbothioyl]-amino}-1,1′-biphenyl;-   B649 (C₂₈H₂₄N₆O₆; MW=540.527):-   3,3′-dimethyl-4,4′-bis{[(4-nitroanilino)carbonyl]amino}-1,1′-biphenyl;-   B650 (C₂₈H₂₄N₆O₄S₂; MW=572.660):-   3,3′-dimethyl-4,4′-bis{[(4-nitroanilino)carbothioyl]-amino}-1,1′-biphenyl;-   B651 (C₁₆H₂₆N₄O₃; MW=322.408):-   N-[4-(diethylamino)-1-methylbutyl]-N′-(4-nitrophenyl)-urea;-   B652 (C₁₆H₂₆N₄O₂S; MW=338.469):-   N-[4-(diethylamino)-1-methylbutyl]-N′-(4-nitrophenyl)-thiourea;-   B653 (C₂₇H₁₉N₇O₆; MW=537.483):-   N′-(6-{[(4-nitroanilino)carbonyl]amino}-3-acridinyl)-N-(4-nitrophenyl)urea;-   B654 (C₂₇H₁₉N₇O₄S₂; MW=569.617):-   N′-(6-{[(4-nitroanilino)carbothioyl]amino}-3-acridinyl)-N-(4-nitrophenyl)thiourea;-   B655 (C₂₁H₂₄Br₂N₄O₃; MW=540.248):-   N-(2,4-dibromo-6-{[cyclohexyl(methyl)amino]methyl}-phenyl)-N′-(4-nitrophenyl)urea;-   B656 (C₂₁H₂₄Br₂N₄O₂S; MW=556.315):-   N-(2,4-dibromo-6-{[cyclohexyl(methyl)amino]methyl}-phenyl)-N′-(4-nitrophenyl)thiourea;-   B657 (C₁₅H₁₆N₄O₃; MW=300.313):-   N-[4-(dimethylamino)phenyl]-N′-(4-nitrophenyl)urea;-   B658 (C₁₅H₁₆N₄ O₂S; MW=316.379):-   N-[4-(dimethylamino)phenyl]-N′-(4-nitrophenyl)thiourea;-   B659 (C_(1l)H₈ClN₅O₃; MW=293.666):-   N-(6-chloro-2-pyrazinyl)-N′-(4-nitrophenyl)urea;-   B660 (c₁₁H₈ClN₅o₂S; MW=309.732):-   N-(6-chloro-2-pyrazinyl)-N′-(4-nitrophenyl)thiourea;-   B661 (C₁₂H₉ClN₄O₃; MW=292.678):-   N-(5-chloro-2-pyridinyl)-N′-(4-nitrophenyl)urea;-   B662 (C₁₂H₉ClN₄O₂S; MW=308.744):-   N-(5-chloro-2-pyridinyl)-N′-(4-nitrophenyl)thiourea;-   B663 (C₁₅H₁₂Cl₂FN₅O; MW=368.193):-   N-[{2-[(E)-(2,6-dichlorophenyl)methylidene]hydrazino}-(imino)methyl]-N′-(4-fluorophenyl)urea;-   B664 (C₁₅H₁₂Cl₂FN₅S; MW=384.259):-   N-[{2-[(E)-(2,6-dichlorophenyl)methylidene]hydrazino}-(imino)methyl]-N′-(4-fluorophenyl)thiourea;-   B665 (C₁₀H₁₁FN₄O₃; MW=254.218):-   2-{[{[(4-fluoroanilino)carbonyl]amino}(imino)methyl]-amino}acetic    acid;-   B666 (C₁₀H₁₁FN₄O₂s; MW=270.284):-   2-{[{[(4-fluoroanilino)carbothioyl]amino}(imino)methyl]amino}acetic    acid;-   B667 (C₁₇H₁₇FN₄O₃; MW=344.340):-   2-({[{[(4-fluoroanilino)carbonyl]amino}(imino)    methyl]-amino}methyl)-2,3-dihydro-1,4-benzodioxine;-   B668 (C₁₇H₁₇FN₄O₂S; MW=360.407):-   2-({[{[(4-fluoroanilino)carbothioyl]amino}(imino)methyl]-amino}methyl)-2,3-dihydro-1,4-benzodioxine;-   B669 (C₁₃H₁₇FN₄O; MW=264.299):-   1-fluoro-4-{[({imino[(3-methyl-2-butenyl)amino]methyl}-amino)carbonyl]amino}benzene;-   B670 (C₁₃H₁₇FN₄S; MW=280.365):-   1-fluoro-4-{[({imino[(3-methyl-2-butenyl)amino]methyl}-amino)carbothioyl]amino}benzene;-   B671 (C₁₇H₂₃FN₄O₃; MW=350.388):-   2-({[{[(4-fluoroanilino)carbonyl]amino}(imino)    methyl]-amino}methyl)-1,4-dioxaspiro[4.5]decane;-   B672 (C₁₇H₂₃FN₄O₂S; MW=366.455):-   2-({[{[(4-fluoroanilino)carbothioyl]amino}(imino)methyl]-amino}methyl)-1,4-dioxaspiro[4.5]decane;-   B673 (C₁₆H₁₃Cl₂FN₄O₂; MW=383.204):-   1,3-dichloro-2-(1-{[{[(4-fluoroanilino)carbonyl]amino}-(imino)methyl]amino}-2-oxoethyl)benzene;-   B674 (C₁₆H₁₃Cl₂FN₄OS; MW=399.271):-   1,3-dichloro-2-(1-{[{[(4-fluoroanilino)carbothioyl]-amino}(imino)    methyl]amino}-2-oxoethyl)benzene;-   B675 (C₉H₈FN₅O; MW=221.191):-   1-[({[(cyanoamino)(imino)methyl]amino}carbonyl)amino]-4-fluorobenzene;-   B676 (C₉H₈FN₅S; MW=237.258):-   1-[({[(cyanoamino)(imino) methyl]amino}carbothioyl)    amino]-4-fluorobenzene;-   B677 (C₁₅H₁₃F₂N₅O₂; MW=333.293):-   N′-[{[(4-fluoroanilino)carbonyl]amino}(imino)methyl]-N-(4-fluorophenyl)urea;-   B678 (C₁₅H₁₃F₂N₅S₂; MW=365.426):-   N′-[{[(4-fluoroanilino)carbothioyl]amino}(imino)methyl]-N-(4-fluorophenyl)thiourea;-   B679 (C₂₂H₂₆F₂N₈O₆; MW=536.377):-   1-fluoro-4-[({[[(3-{[{[(4-fluoroanilino)carbonyl]amino}-(imino)methyl]amino}-2,4,5,6-tetrahydroxycyclohexyl)-amino](imino)    methyl]amino}carbonyl) amino]benzene;-   B680 (C₂₂H₂₆F₂N₈O₄S₂; MW=568.510):-   1-fluoro-4-[({[[(3-{[{[(4-fluoroanilino) carbothioyl]-amino}(imino)    methyl]amino}-2,4,5,6-tetrahydroxycyclohexyl)amino](imino)methyl]amino}carbothioyl)amino]benzene;-   B681 (C₂₁H₁₆FN₇O₇; MW=497.393):-   N-(4-fluorophenyl)-N′-[imino(2-{(E)-3-(5-nitro-2-furyl)-1-[(E)-2-(5-nitro-2-furyl)ethenyl]-2-propenylidene}hydrazino)methyl]urea;-   B682 (C₂₁H₁₆FN₇O₆S; MW=513.460):-   N-(4-fluorophenyl)-N′-[imino(2-{(E)-3-(5-nitro-2-furyl)-1-[(E)-2-(5-nitro-2-furyl)ethenyl]-2-propenylidene}hydrazino)methyl]thiourea.

Other typical compounds according to the present invention are comprisedby the general formula (I) and have Y as defined above and R selectedfrom said group (b). Thus, they have the following general formula (IV),as depicted in Table 2 hereinbelow.

TABLE 2 (IV)

Y R₃ R₄/R₅ R₆ Denoted O 4-nitro- 5-bromo-2- 6-nitro-1,3- B35-4 phenylpyridinyl benzothiazol-2-yl S 4-nitro- 6-chloro-2- 6-nitro-1,3- B35-5phenyl pyrazinyl benzothiazol-2-yl O 4-nitro- 6-chloro-2- 6-nitro-1,3-B35-6 phenyl pyridinyl benzothiazol-2-yl S phenyl (4-nitrophenyl)-6-nitro-1,3- B36 sulfonyl benzothiazol-2-yl S 4-nitro- (4-nitrophenyl)-6-nitro-1,3- B36-2 phenyl sulfonyl benzothiazol-2-yl O 4-nitro-(4-nitrophenyl)- 6-nitro-1,3- B36-3 phenyl sulfonyl benzothiazol-2-yl S4-nitro- (4-nitrophenyl)- 3,5-dicarboxyphenyl B37-3 phenyl sulfonyl S4-fluoro- (4-nitrophenyl)- 3,5-dicarboxyphenyl B37-4 phenyl sulfonyl S4-fluoro- 5-bromo-2-pyridinyl/ 3,5-dicarboxyphenyl B37-5 phenyl6-bromo-2-pyridinyl S 4-fluoro- 6-chloro-2- 3,5-dicarboxyphenyl B37-6phenyl pyrazinyl S 4-fluoro- 6-chloro-2- 3,5-dicarboxyphenyl B37-7phenyl pyridinyl S 4-nitro- 6-chloro-2- 3,5-dicarboxyphenyl B37-8 phenylpyridinyl S 4-fluoro- (4-nitrophenyl)- 6-nitro-1,3- B42 phenyl sulfonylbenzothiazol-2-yl S 4-fluoro- 6-chloro-2- 6-nitro-1,3- B42-2 phenylpyrazinyl benzothiazol-2-yl S 4-fluoro- 6-chloro-2- 6-nitro-1,3- B42-3phenyl pyridinyl benzothiazol-2-yl S 3,4-dicar- (4-nitrophenyl)-1,3-benzothiazol- B42-30 boxyphenyl sulfonyl 2-yl S 4-[(4-car-(4-nitrophenyl)- 6-nitro-1,3- B42-31 boxyanilino)- sulfonylbenzothiazol-2-yl sulfonyl]- phenyl S 8-chloro- (4-nitrophenyl)-1,3-benzothiazol- B42-33 5-quinolinyl sulfonyl 2-yl S 8-chloro-(4-nitrophenyl)- 8-chloro-5- B42-34 5-quinolinyl sulfonyl quinolinyl S3-chloro- (4-fluorophenyl)- 6-chloro-2- B42-35 4-pyridinyl sulfonylpyrazinyl S 3-chloro- (4-fluorophenyl)- 3-(trifluoro- B42-26 4-pyridinylsulfonyl methyl)phenyl S 4-fluoro- (4-nitrophenyl)- (4-methylphenyl)-B42-37 phenyl sulfonyl sulfonyl S 4-fluoro- (4-nitrophenyl)-[5-(dimethyl- B42-38 phenyl sulfonyl amino)-1- naphthyl]sulfonyl S4-fluoro- (4-nitrophenyl)- (7-fluoro-2,1,3- B42-39 phenyl sulfonylbenzoxadiazol-4- yl)sulfonyl S 4-fluoro- (4-nitrophenyl)- 6-methyl-1,1-B42-40 phenyl sulfonyl dioxo-1,2,3,4- tetrahydro-1λ⁶- thiochromene-7-sulfonyl S 3-nitro- phenylsulfonyl 6-nitro-1,3- B43 phenylbenzothiazol-2-yl S phenyl (4-nitrophenyl)- 4-carboxy-2,6- B49-2sulfonyl diiodophenyl S phenyl (4-fluorophenyl)- 4-carboxy-2,6- B49-3sulfonyl diiodophenyl S 4-nitro- (4-fluorophenyl)- 4-carboxy-2,6- B49-4phenyl sulfonyl diiodophenyl S 4-nitro- (4-nitrophenyl)- 4-carboxy-2,6-B49-5 phenyl sulfonyl diiodophenyl S 4-fluoro- (4-nitrophenyl)-4-carboxy-2,6- B49-6 phenyl sulfonyl diiodophenyl S phenyl 5-bromo-2-4-carboxy-2,6- B49-7 pyridinyl diiodophenyl S phenyl 6-chloro-2-4-carboxy-2,6- B49-8 pyrazinyl diiodophenyl S 4-nitro- 6-chloro-2-4-carboxy-2,6- B49-9 phenyl pyrazinyl diiodophenyl S 4-nitro-2-pyrazinyl 4-carboxy-2,6- B49-10 phenyl diiodophenyl S 4-fluoro-2-pyrazinyl 4-carboxy-2,6- B49-11 phenyl diiodophenyl S 4-fluoro-6-chloro-2- 4-carboxy-2,6- B49-12 phenyl pyrazinyl diiodophenyl S4-fluoro- 6-chloro-2- 4-carboxy-2,6- B49-13 phenyl pyridinyldiiodophenyl S 4-nitro- 6-chloro-2- 4-carboxy-2,6- B49-15 phenylpyridinyl diiodophenyl S carboxy- (trifluoro- 4-carboxy-2,6- B49-31methyl methyl)sulfonyl diiodophenyl S phenethyl 2-naphthyl-4-carboxy-2,6- B49-33 sulfonyl diiodophenyl S 4-carboxy- 2-naphthyl-4-carboxy-2,6- B49-34 3-hydroxy- sulfonyl diiodophenyl phenyl S2,3-diio- (4-nitrophenyl)- 4-carboxy-2,6- B49-40 dopropyl sulfonyldiiodophenyl S 4-cyano- 6-chloro-2-pyridinyl/ 4-nitrophenyl B51-2 phenyl5-chloro-2-pyridinyl S 4-cyano- 6-chloro-2- 4-nitrophenyl B51-3 phenylpyrazinyl S 4-cyano- 5-bromo-2- 4-nitrophenyl B51-4 phenyl pyridinyl S4-cyano- (4-nitrophenyl)- 4-nitrophenyl B51-5 phenyl sulfonyl S 4-cyano-(trifluoro- 4-nitrophenyl B51-6 phenyl methyl)sulfonyl S 4-cyano-(trifluoro- 4-fluorophenyl B51-7 phenyl methyl)sulfonyl S phenyl(4-nitrophenyl)- 3,4,5-trimethoxy- B56 sulfonyl phenyl S 4-nitro-(4-nitrophenyl)- 4-isopropylphenyl B57 phenyl sulfonyl S 4-nitro-3-chloro-2- 2-(4-morpholinyl)- B61-3 phenyl pyridinyl ethyl S 4-nitro-6-chloro-2- 2-(4-morpholinyl)- B61-4 phenyl pyrazinyl ethyl S 4-nitro-(4-nitrophenyl)- 2-(4-morpholinyl)- B61-5 phenyl sulfonyl ethyl S4-nitro- (trifluoro- 2-(4-morpholinyl)- B61-6 phenyl methyl)sulfonylethyl O 4-nitro- (4-nitrophenyl)- 1-carboxy- B304 phenyl sulfonylcyclopentyl O 4-nitro- (4-nitrophenyl)- 3-carboxyphenyl B309 phenylsulfonyl O 4-nitro- (4-nitrophenyl)- 2-trifluoromethyl- B310 phenylsulfonyl 4-nitrophenyl O 4-nitro- (4-fluoro- 4-trifluoromethyl- B313phenyl phenyl)sulfonyl 2-nitrophenyl O 4-nitro- (4-fluoro- 4-chloro-3-B314 phenyl phenyl)sulfonyl (trifluoromethyl)- phenyl S 4-nitro-5-chloro-2-pyrazinyl/ 2,2,2-trifluoroethyl B324 phenyl6-chloro-2-pyrazinyl S 4-nitro- (4-nitrophenyl)- 2,2,2-trifluoroethylB323 phenyl sulfonyl O 4-nitro- 5-chloro-2-pyrazinyl/2,2,2-trifluoroethyl B325 phenyl 6-chloro-2-pyrazinyl O 4-nitro-ethylsulfonyl 4-(trifluoromethyl)- B327 phenyl phenyl O 4-nitro-6-chloro-2- 4-(trifluoromethyl)- B328 phenyl pyrazinyl phenyl S 4-nitro-(4-nitrophenyl)- 1-(3,4-dihydroxy- B338 phenyl sulfonyl5-(hydroxymethyl)- tetrahydro-2- furanyl)-5-iodo- 2(1H)-3- pyrimidinyl S4-nitro- 6-chloro-2- 1-[3,4-dihydroxy- B339 phenyl pyrazinyl5-(hydroxymethyl)- tetrahydro-2- furanyl]-5-iodo- 2-oxo-1,2-dihydro-4-pyrimidinyl S 4-nitro- (trifluoromethyl)- 2-carboxybicyclo- B353phenyl sulfonyl [2.2.1]heptanyl O 4-nitro- 6-chloro-2- (4-carboxy- B355phenyl pyrazinyl cyclohexyl)methyl O 4-nitro- (4-nitrophenyl)-3-carboxyadamantyl B360 phenyl sulfonyl O 4-nitro- (4-nitrophenyl)-1,3,3- B363-2 phenyl sulfonyl tricarboxypropyl S 4-nitro-(4-nitrophenyl)- 1-carboxy- B370 phenyl sulfonyl cyclopropyl O 4-nitro-(4-nitrophenyl)- 1-(3,4-dihydroxy- B600 phenyl sulfonyl1-(1-carboxyethyl)- butoxy)-2-oxo-ethyl O 4-nitro- (4-nitrophenyl)-6-((1R,2S)-1,2,3- B603 phenyl sulfonyl trihydroxypropyl)-4(8H)-2-pteridinenyl O 4-nitro- (4-nitrophenyl)- 2,4,5-trihydroxy- B605phenyl sulfonyl phenethyl S same as (4-nitrophenyl)- 3-{1-[(4-nitro-B800 R₆ sulfonyl phenyl)sulfonyl]- 4,5-dihydro-1H- imidazol-2-yl}-phenyl O (4-methyl- (4-nitrophenyl)- hexahydrocyclo- B801 phenyl)-sulfonyl penta[c]pyrrol- sulfonyl 2(1H)-yl O 4-nitro- (4-fluoro-(4-pyridinyl)- B802 phenyl phenyl)sulfonyl sulfonyl O cyclohexyl(4-nitrophenyl)- [4-(2-{(5-chloro- B803 sulfonyl 2-methoxybenzoyl)-[(4-nitrophenyl)- sulfonyl]amino}- ethyl)phenyl]- sulfonyl O cyclohexyl(4-nitrophenyl)- 4-(2-{((5-methyl-2- B804 sulfonyl pyrazinyl)carbonyl)-((4-nitrophenyl)- sulfonyl)amino}- ethyl)- benzenesulfonyl O cyclohexyl(4-nitrophenyl)- (4-{2-[7-methoxy- B805 sulfonyl 4,4-dimethyl-1,3-dioxo-3,4-dihydro- 2(1H)-isoquinolin- yl]ethyl}phenyl)- sulfonyl ON-azepanyl (4-nitrophenyl)- 4-(2-{((5-methyl-3- B806 sulfonylisoxazolyl)- carbonyl)((4- nitrophenyl)- sulfonyl)amino}- ethyl)-benzenesulfonyl O (4-methyl- 4-nitrophenyl 3-hydroxy-4,7,7- B807phenyl)- trimethylbicyclo- sulfonyl [2.2.1]hept-2-yl O butyl(4-nitrophenyl)- (4-{[(4- B808 sulfonyl nitrophenyl)- sulfonyl]amino}-phenyl)sulfonyl O cyclohexyl (4-nitrophenyl)- 2,3-dihydro-1H- B809sulfonyl inden-5-yl-sulfonyl O 4-nitro- (4-fluoro- (4-pyridinyl)- B810phenyl phenyl)sulfonyl sulfonyl

Compound data and systematic names for the compounds presented in Table2 are as follows:

-   B35-4 (C₂₄H₁₃Br₂N₇O₅S; MW=671.278):-   N,N′-bis    (5-bromo-2-pyridinyl)-N-(6-nitro-1,3-benzothiazol-2-yl)-N′-(4-nitrophenyl)urea;-   B35-5 (C₂₂H₁₁Cl₂N₉O₄S₂; MW=600.418):-   N,N′-bis    (6-chloro-2-pyrazinyl)-N-(6-nitro-1,3-benzothiazol-2-yl)-N′-(4-nitrophenyl)thiourea;-   B35-6 (C₂₄H₁₃Cl₂N₇O₅S; MW=582.376):-   N,N′-bis(6-chloro-2-pyridinyl)-N-(6-nitro-1,3-benzothiazol-2-yl)-N′-(4-nitrophenyl)urea;-   B36 (C₂₆H₁₆N₆0₁₀S₄; MW=700.704):-   4-nitro-N-(6-nitro-1,3-benzothiazol-2-yl)-N-({[(4-nitro-phenyl)    sulfonyl]anilino}carbothioyl)benzenesulfonamide;-   B36-2 (C₂₆H₁₅N₇O₁₂S₄; MW=745.701):-   4-nitro-N-(6-nitro-1,3-benzothiazol-2-yl)-N-({4-nitro[(4-nitrophenyl)sulfonyl]anilino}carbothioyl)benzenesulfonamide;-   B36-3 (C₂₆H₁₆N₆O₁₁S₃; MW=684.637):-   4-nitro-N-(6-nitro-1,3-benzothiazol-2-yl)-N-({4-nitro    [(4-nitrophenyl)sulfonyl]anilino}carbonyl)benzenesulfonamide;-   B37-3 (C₂₇H₁₇N₅O₁₄S₃; MW=731.647):-   5-{({4-nitro[(4-nitrophenyl)sulfonyl]anilino}carbothioyl)[(4-nitrophenyl)sulfonyl]amino}isophthalic    acid;-   B37-4 (C₂₇H₁₇FN₄O₁₂S₃; MW=704.640):-   5-{({4-fluoro[(4-nitrophenyl)sulfonyl]anilino}carbothioyl)[(4-nitrophenyl)sulfonyl]amino}isophthalic    acid;-   B37-5 (C₂₅H₁₅Br₂FN₄O₄S; MW=646.284):-   5-((6-bromo-2-pyridinyl){[(5-bromo-2-pyridinyl)-4-fluoroanilino]carbothioyl}amino)isophthalic    acid;-   B37-6 (C₂₃H₁₃Cl₂FN₆O₄S; MW=559.357):-   5-((6-chloro-2-pyrazinyl){[(6-chloro-2-pyrazinyl)-4-fluoroanilino]carbothioyl}amino)isophthalic    acid; B37-7 (C₂sH₁₅Cl₂FN₄O₄S; MW=557.381):-   5-((6-chloro-2-pyridinyl){[(6-chloro-2-pyridinyl)-4-fluoroanilino]carbothioyl}amino)isophthalic    acid;-   B37-8 (C₂₅H₁₅Cl₂N₅O₆S; MW=584.388):-   5-((6-chloro-2-pyridinyl){[(6-chloro-2-pyridinyl)-4-nitroanilino]carbothioyl}amino)isophthalic    acid;-   B42 (C₂₆H₁₅FN₆O₁₀S₄; MW=718.694):-   N-(4-fluorophenyl)-4-nitro-N-({(6-nitro-1,3-benzothiazol-2-yl)[(4-nitrophenyl)sulfonyl]amino}carbothioyl)benzene-sulfonamide;-   B42-2 (C₂₂H₁₁Cl₂FN₈O₂S₂; MW=73.411):-   N,N′-bis(6-chloro-2-pyrazinyl)-N-(4-fluorophenyl)-N′-(6-nitro-1,3-benzothiazol-2-yl)thiourea;-   B42-3 (C₂₄H₁₃Cl₂FN₆O₂S₂; MW=571.435):-   N,N′-bis(6-chloro-2-pyridinyl)-N-(4-fluorophenyl)-N′-(6-nitro-1,3-benzothiazol-2-yl)thiourea;-   B42-30 (C₂₈H₁₇N₅O₁₂S₄; MW=743.725):-   4-{({(1,3-benzothiazol-2-yl)[(4-nitrophenyl)sulfonyl]-amino}carbothioyl)[(4-nitrophenyl)sulfonyl]amino}-phthalic    acid;-   B42-31 (C₃₃H₂₁N₇O₁₄S₂; MW=899.889):-   4-{[(4-{({(6-nitro-1,3-benzothiazol-2-yl)[(4-nitrophen-yl)sulfonyl]amino}carbothioyl)[(4-nitrophenyl)sulfonyl]-amino}phenyl)sulfonyl]amino}benzoic    acid;-   B42-33 (C₂₉H₁₇ClN₆O₈S₄; MW=741.198):-   N-(1,3-benzothiazol-2-yl)-N-({(8-chloro-5-quinolinyl)[(4-nitrophenyl)sulfonyl]amino}carbothioyl)-4-nitro-benzenesulfonamide;-   B42-34 (C₃₁H₁₈Cl₂N₆O₈S₃; MW=769.614):-   N-(8-chloro-5-quinolinyl)-N-({(8-chloro-5-quinolinyl)[(4-nitrophenyl)sulfonyl]amino}carbothioyl)-4-nitrobenzene-sulfonamide;-   B42-35 (C₂₂H₁₃Cl₂F₂N₅O₄S₃; MW=616.470):-   N-({(6-chloro-2-pyrazinyl)[(4-fluorophenyl)sulfonyl]amino}carbothioyl)-N-(3-chloro-4-pyridinyl)-4-fluorobenzene-sulfonamide;-   B42-36 (C₂₅H₁₅ClF₅N₃O₄S₃; MW=648.047):-   N-(3-chloro-4-pyridinyl)-4-fluoro-N-{[[(4-fluorophenyl)-sulfonyl]-3-(trifluoromethyl)anilino]carbothioyl}benzene-sulfonamide;-   B42-37 (C₂₆H₁₉FN₄O₁₀S₄; MW=694.712):-   N-({4-fluoro[(4-nitrophenyl)sulfonyl]anilino}carbothioyl)-N-[(4-methylphenyl)sulfonyl]-4-nitrobenzenesulfonamide;-   B42-38 (C₂₇H₂₂FN₅O₁₀S₄; MW=723.754):-   N-{[5-(dimethylamino)-1-naphthyl]sulfonyl}-N-({4-fluoro[(4-nitrophenyl)sulfonyl]anilino}carbothioyl)-4-nitrobenzenesulfonamide;-   B42-39 (C₂₅H₁₄F₂N₆O₁₁S₄; MW=740.673):-   N-[(7-fluoro-2,1,3-benzoxadiazol-4-yl)sulfonyl]-N-({4-fluoro[(4-nitrophenyl)sulfonyl]anilino}carbothioyl)-4-nitrobenzenesulfonamide;-   B42-40 (C₂₉H₂₃FN₄O₁₂S₅; MW=798.841):-   N-({4-fluoro[(4-nitrophenyl)sulfonyl]anilino}carbothioyl)-N-[(6-methyl-1,1-dioxo-1,2,3,4-tetrahydro-1λ⁶-thiochromen-7-yl)sulfonyl]-4-nitrobenzenesulfonamide;-   B43 (C₂₆H₁₇N₅O₈S₄; MW=655.706):-   N-{[(6-nitro-1,3-benzothiazol-2-yl)    (phenylsulfonyl)amino]carbothioyl}-N-(3-nitrophenyl)    benzenesulfonamide;-   B49-2 (C₂₆H₁₆I₂N₄O₁₀S₃; MW=894.433):-   3,5-diiodo-4-[[(4-nitrophenyl)sulfonyl]({[(4-nitrophenyl)sulfonyl]anilino}carbothioyl)amino]benzoic    acid;-   B49-3 (C₂₆H₁₆F₂I₂N₂O₆S₃; MW=840.419):-   4-[[(4-fluorophenyl)sulfonyl]({[(4-fluorophenyl)sulfonyl]anilino}carbothioyl)amino]-3,5-diiodobenzoic    acid;-   B49-4 (C₂₆H₁₅F₂I₂N₃O₈S₃; MW=885.416):-   4-[[(4-fluorophenyl)sulfonyl]({[(4-fluorophenyl)sulfonyl]-4-nitroanilino}carbothioyl)amino]-3,5-diiodobenzoic    acid;-   B49-5 (C₂₆H₁₅I₂N₅O₁₂S₃; MW=939.431):-   3,5-diiodo-4-{({4-nitro[(4-nitrophenyl)sulfonyl]anilino}-carbothioyl)[(4-nitrophenyl)    sulfonyl]amino}benzoic acid;-   B49-6 (C₂₆H₁₅FI₂N₄O₁₀S₃; MW=912.424):-   4-{({4-fluoro[(4-nitrophenyl)sulfonyl]anilino}carbothioyl)[(4-nitrophenyl)sulfonyl]amino}-3,5-diiodobenzoic    acid;-   B49-7 (C₂₄H₁₄Br₂I₂N₄O₂S; MW=836.077):-   4-((5-bromo-2-pyridinyl){[(5-bromo-2-pyridinyl)anilino]-carbothioyl}amino)-3,5-diiodobenzoic    acid;-   B49-8 (C₂₂H₁₂Cl₂I₂N₆O₂S; MW=749.150):-   4-((6-chloro-2-pyrazinyl){[(6-chloro-2-pyrazinyl)-anilino]carbothioyl}amino)-3,5-diiodobenzoic    acid;-   B49-9 (C₂₂H₁₁Cl₂I₂N₇O₄S; MW=794.148):-   4-((6-chloro-2-pyrazinyl){[(6-chloro-2-pyrazinyl)-4-nitroanilino]carbothioyl}amino)-3,5-diiodobenzoic    acid;-   B49-10 (C₂₂H₁₃I₂N₇O₄S; MW=725.258):-   3,5-diiodo-4-[{[4-nitro(2-pyrazinyl)anilino]carbothioyl}-(2-pyrazinyl)amino]    benzoic acid;-   B49-11 (C₂₂H₁₃FI₂N₆O₂S; MW=698.251):-   4-[{[4-fluoro(2-pyrazinyl)anilino]carbothioyl}(2-pyrazinyl)amino]-3,5-diiodobenzoic    acid;-   B49-12 (C₂₂H₁₁Cl₂FI₂N₆O₂S; MW=767.141):-   4-((6-chloro-2-pyrazinyl){[(6-chloro-2-pyrazinyl)-4-fluoroanilino]carbothioyl}amino)-3,5-diiodobenzoic    acid;-   B49-13 (C₂₄H₂₃Cl₂FI₂N₄O₂S; MW=765.164):-   4-((6-chloro-2-pyridinyl){[(6-chloro-2-pyridinyl)-4-fluoroanilino]carbothioyl}amino)-3,5-diiodobenzoic    acid;-   B49-15 (C₂₄H₁₃Cl₂I₂N₅O₄s; MW=792.172):-   4-((6-chloro-2-pyridinyl){[(6-chloro-2-pyridinyl)-4-nitroanilino]carbothioyl}amino)-3,5-diiodobenzoic    acid;-   B49-31 (C₁₂H₆F₆I₂N₂O₈S₃; MW=770.182):-   4-{({(carboxymethyl)[(trifluoromethyl)sulfonyl]amino}-carbothioyl)[(trifluoromethyl)sulfonyl]amino}-3,5-diiodobenzoic    acid;-   B49-33 (C₃₆H₂₆I₂N₂O₆S₃; MW=932.608):-   3,5-diiodo-4-((2-naphthylsulfonyl){[(2-naphthylsulfonyl)-(phenethyl)amino]carbothioyl}amino)benzoic    acid;-   B49-34 (C₃₅H₂₂I₂N₂O₉S₃; MW=964.564):-   4-[{[4-carboxy-3-hydroxy(2-naphthylsulfonyl)anilino]carbothioyl}(2-naphthylsulfonyl)amino]-3,5-diiodobenzoic    acid;-   B49-40 (C₂₃H₁₆I₄N₄O₁₀S₃; MW=1112.210):-   4-{({(2,3-diiodopropyl)[(4-nitrophenyl)sulfonyl]amino}-carbothioyl)[(3-nitrophenyl)sulfonyl]amino}-3,5-diiodo-benzoic    acid;-   B51-2 (C₂₄H₁₄Cl₂N₆O₂S; MW=521.379):-   N-(5-chloro-2-pyridinyl)-N′-(6-chloro-2-pyridinyl)-N′-(4-cyanophenyl)-N-(4-nitrophenyl)thiourea;-   B51-3 (C₂₂H₁₂Cl₂N₈O₂S; MW=523.355):-   N,N′-bis(6-chloro-2-pyrazinyl)-N-(4-cyanophenyl)-N′-(4-nitrophenyl)thiourea;-   B51-4 (C₂₄H₁₄Br₂N₆O₂S; MW=610.281):-   N,N′-bis(5-bromo-2-pyridinyl)-N-(4-cyanophenyl)-N′-(4-nitrophenyl)thiourea;-   B51-5 (C₂₆H₁₆N₆O₁₀S₃; MW=668.638):-   N-({4-cyano[(4-nitrophenyl)sulfonyl]anilino}carbothioyl)-4-nitro-N-(4-nitrophenyl)benzenesulfonamide;-   B51-6 (C₁₆H₈F₆N₄O₆S₃; MW=562.447):-   N-(4-cyanophenyl)    (trifluoro)-N-({4-nitro[(trifluoromethyl)sulfonyl]anilino}carbothioyl)    methanesulfonamide;-   B51-7 (C₁₆H₈F₇N₃O₄S₃; MW=535.439):-   N-(4-cyanophenyl)(trifluoro)-N-({4-fluoro[(trifluoromethyl)sulfonyl]anilino}carbothioyl)    methanesulfonamide;-   B56 (C₂₈H₂₄N₄O₁₁S3; MW=688.708):-   4-nitro-N-({[(4-nitrophenyl)sulfonyl]anilino}carbothioyl)-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide;-   B57 (C₂₈H₂₃N₅O₁₀S₃; MW=685.708):-   N-({4-isopropyl    [(4-nitrophenyl)sulfonyl]anilino}carbothioyl)-4-nitro-N-(4-nitrophenyl)benzenesulfonamide;-   B61-3 (C₂₃H₂₂Cl₂N₆O₃S; MW=533.431):-   N,N′-bis(3-chloro-2-pyridinyl)-N-[2-(4-morpholinyl)-ethyl]-N′-(4-nitrophenyl)thiourea;-   B61-4 (C₂₁H₂₀Cl₂N₈O₃S; MW=535.407):-   N,N′-bis(6-chloro-2-pyrazinyl)-N-[2-(4-morpholinyl)-ethyl]-N′-(4-nitrophenyl)thiourea;-   B61-5 (C₂₅H₂₄N₆O₁₃S₃; MW=680.690):-   N-[2-(4-morpholinyl)ethyl]-4-nitro-N-({4-nitro[(4-nitro-phenyl)sulfonyl]anilino}carbothioyl)benzenesulfonamide;-   B61-6 (C₁₅H₁₆F₆N₄O₇S₃; MW=574.499):-   trifluoro-N-[2-(4-morpholinyl)ethyl]-N-({4-nitro[(trifluoromethyl)sulfonyl]anilino}carbothioyl)    methanesulfonamide;-   B304 (C₂₅H₂₃N₃09S₂; MW=573.597):-   1-{({4-nitro[(4-nitrophenyl)sulfonyl]anilino}carbonyl)-[(4-nitrophenyl)sulfonyl]amino}cyclopentanecarboxylic    acid;-   B309 (C₂₆H₁₇N₅O₁₃S₂; MW=671.571):-   3-{({4-nitro[(4-nitrophenyl)sulfonyl]anilino}carbonyl)-[(4-nitrophenyl)sulfonyl]amino}benzoic    acid;-   B310 (C₂₆H₁₅F₃N₆O₃S₂; MW=740.557):-   4-nitro-N-{[4-nitro[(4-nitrophenyl)sulfonyl]1-2-(trifluoromethyl)anilino]carbonyl}-N-(4-nitrophenyl)benzene-sulfonamide;-   B313 (C₂₆H₁₅F₅N₄O₉S₂; MW=686.543):-   4-fluoro-N-{[[(4-fluorophenyl)sulfonyl]-2-nitro-4-(trifluoromethyl)anilino]carbonyl}-N-(4-nitrophenyl)benzene-sulfonamide;-   B314 (C₂₆H₁₅ClF₅N₃O₇S₂; MW=675.990):-   N-{[4-chloro[(4-fluorophenyl)sulfonyl]-3-(trifluoromethyl)anilino]carbonyl}-4-fluoro-N-(4-nitrophenyl)benzene-sulfonamide;-   B323 (C₂₁H₁₄F₃N₅O₁₀S₃; MW=649.557):-   4-nitro-N-(4-nitrophenyl)-N-{[[(4-nitrophenyl)sulfonyl]-(2,2,2-trifluoroethyl)amino]carbotiohyl}benzenesulfonamide;-   B324 (C₁₇H₁₀Cl₂F₃N₇O₂S; MW=504.274):-   N-(5-chloro-2-pyrazinyl)-N′-(6-chloro-2-pyrazinyl)-N-(4-nitrophenyl)-N′-(2,2,2-trifluoroethyl)thiourea;-   B325 (C₁₇H₁₀Cl₂F₃N₇O₃; MW=488.207):-   N-(5-chloro-2-pyrazinyl)-N′-(6-chloro-2-pyrazinyl)-N-(4-nitrophenyl)-N′-(2,2,2-trifluoroethyl)urea;-   B327 (C₁₈H₁₈F₃N₃O₀S₂; MW=509.479):-   N-{[(ethylsulfonyl)-4-nitroanilino]carbonyl}-N-[4-(trifluoromethyl)phenyl]-1-ethanesulfonamide;-   B328 (C₂₂H₁₂Cl₂F₃N₇O₃; MW=550.277):-   N,N′-bis    (6-chloro-2-pyrazinyl)-N-(4-nitrophenyl)-N′-[4-(trifluoromethyl)phenyl]urea;-   B338 (C₂₈H₂₂IN₇O₁₅S₃; MW=919.615):-   N-({{1-[3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-iodo-2-oxo-1,2-dihydro-4-pyrimidinyl}[(4-nitrophenyl)sulfonyl]amino}carbothioyl)-4-nitro-N-(4-nitrophenyl)benzenesulfonamide;-   B339 (C₂₄H₁₈Cl₂N₉O₇S; MW=774.332):-   N,N′-bis(6-chloro-2-pyrazinyl)-N-{1-[3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-iodo-2-oxo-1,2-dihydro-4-pyrimidinyl}-N′-(4-nitrophenyl)    thiourea;-   B353 (C₁₇H₁₅F₆N₃O₈S₃; MW=599.505):-   3-{({4-nitro[(trifluoromethyl)sulfonyl]anilino}carbothioyl)[(trifluoromethyl)sulfonyl]amino}bicyclo    [2.2.1]-heptane-2-carboxylic acid;-   B355 (C₂₃H₂₁Cl₂N₇₀s; MW=546.362):-   4-[((6-chloro-2-pyrazinyl){[(6-chloro-2-pyrazinyl)-4-nitroanilino]carbonyl}amino)methyl]cyclohexanecarboxylic    acid;-   B360 (C₃₀H₂₇N₅O₁₃S₂; MW=729.693)-   3-{({4-nitro[(3-nitrophenyl)sulfonyl]anilino}carbonyl)[(4-nitrophenyl)sulfonyl]amino}-1-adamantanecarboxylic    acid;-   B363-2 (C₂₅H₁₉N₅O₁₇S₂; MW=725.574):-   3-{({4-nitro[(4-nitrophenyl)sulfonyl]anilino}carbonyl)[(4-nitrophenyl)sulfonyl]amino}-1,1,3-propanetricarboxylic    acid;-   B370 (C₂₃H₁₇N₅O₁₂S₃; MW=651.606):-   1-{({4-nitro[(4-nitrophenyl)sulfonyl]anilino}carbothioyl)[(4-nitrophenyl)sulfonyl]amino}cyclopropanecarboxylic    acid;-   B600 (C₂₈H₂₇N₅O₁₇S₂; MW=769.669):-   2-[3,4-dihydroxy-1-(1-{({4-nitro[(4-nitrophenyl)sulfonyl]anilino}carbonyl)[(4-nitrophenyl)sulfonyl]amino}-2-oxoethyl)butoxy]propanoic    acid;-   B603 (C₂₈H₂₁N₉O₁₅S₂; MW=787.650):-   12-(4-nitrophenyl)-4,9,9,11,13,13-hexaoxo-10-{4-oxo-6-[(1R,2S)-1,2,3-trihydroxypropyl]-4,8-dihydro-2-pteridinyl)benzenesulfonamide;-   B605 (C₂₇H₂₁N₅O₁₄S₂; MW=703.613):-   4-nitro-N-({4-nitro[(4-nitrophenyl)sulfonyl]anilino}carbonyl)-N-(2,4,5-trihydroxyphenethyl)benzenesulfonamide;-   B800 (C₄₃H₃₂N₁₀O₁₆S₅; MW=1105.102):-   4-nitro-N-(3-{1-[(4-nitrophenyl)sulfonyl]-4,5-dihydro-1H-imidazol-2-yl}phenyl)-N-[([(4-nitrophenyl)sulfonyl]-3-{1-[(4-nitrophenyl)sulfonyl]-4,5-dihydro-1H-imidazol-2-yl}anilino)carbothioyl]benzenesulfonamide;-   B801 (C₂₇H₂₇N₅O₁₁S₃; MW=693.728):-   N-hexahydrocyclopenta[c]pyrrol-2(1H)-yl-N-({[(4-methyl-phenyl)sulfonyl][(4-nitrophenyl)sulfonyl]amino}carbonyl)-4-nitrobenzenesulfonamide;-   B802 (C₂₄H₁₆F₂N₄O₉S₃; MW=638.600):-   N-[(4-fluorophenyl)sulfonyl]-N-({[(4-fluorophenyl)    sulfonyl]-4-nitroanilino}carbonyl)-4-pyridinesulfonamide;-   B803 (C₄₁H₃₇ClN₆O₁₇S₄; MW=1049.479):-   N-({{[4-(2-{(5-chloro-2-methoxybenzoyl)[(4-nitrophenyl)-sulfonyl]amino}ethyl)phenyl]sulfonyl}[(4-nitrophenyl)sulfonyl]amino}carbonyl)-N-cyclohexyl-4-nitrobenzenesulfonamide;-   B804 (C₃₉H₃₆N₈O₁₆S₄; MW=1001.011):-   N-({cyclohexyl[(4-nitrophenyl)sulfonyl]amino}carbonyl)-4-(2-{[(5-methyl-2-pyrazinyl)carbonyl][(4-nitrophenyl)-sulfonyl]amino}ethyl)-N-[(4-nitrophenyl)    sulfonyl]benzene-sulfonamide;-   B805 (C₃₉H₃₉N₅O₁₄S₃; MW=897.950):-   N-({cyclohexyl[(4-nitrophenyl)sulfonyl]amino}carbonyl)-4-{2-[7-methoxy-4,4-dimethyl-1,3-dioxo-3,4-dihydro-2(1H)-isoquinolinyl]ethyl}-N-[(4-nitrophenyl)sulfonyl]benzene-sulfonamide;-   B806 (C₃₈H₃₆N₈O₁₇S₄; MW=1005.000):-   N-(1-azepanyl)-N-({{[4-(2-{[(5-methyl-3-isoxazolyl)carbonyl][(4-nitrophenyl)sulfonyl]amino}ethyl)phenyl]sulfonyl}[(4-nitrophenyl)sulfonyl]amino}carbonyl)-4-nitrobenzenesulfonamide;-   B807 (C₃₀H₃₂N₄O₈S; MW=608.663):-   ({[(3-hydroxy-4,7,7-trimethylbicyclo[2.2.1]hept-2-yl)-4-nitroanilino]carbonyl}-4-nitroanilino)(4-methylphenyl)di-oxo-λ⁶-sulfane;-   B808 (C₂₉H₂₆N₆O₁₅S₄; MW=826.812):-   N-butyl-4-nitro-N-({[(4-nitrophenyl)sulfonyl][(4-nitro-phenyl)sulfonyl]amino}phenyl)sulfonyl]amino}carbonyl)-benzenesulfonamide;-   B809 (C₂₈H₂₈N₄O₁₁S₃; MW=692.740):-   N-({cyclohexyl[(4-nitrophenyl)sulfonyl]amino}carbonyl)-N-(2,3-dihydro-1H-inden-5-yl-sulfonyl)-4-nitrobenzenesulfonamide;-   B810 (C₂₄H₁₆F₂N₄O₉S₃; MW=638.600):-   N-[(4-fluorophenyl)sulfonyl]-N-({[(4-fluorophenyl)sulfonyl]-4-nitroanilino}carbonyl)-4-pyridinesulfonamide.

Some other typical compounds according to the present invention aredepicted in Table 3 below. They correspond to Y as defined above and Rselected from said group (c) and have the general formula (V).

TABLE 3 (V)

R₇ Y R₃ R₄ R₈ (4-N-linked) Denoted S 4-nitro- H piperazin-1-yl{[(4-nitrophenyl)- B45 phenyl amino]carbothioyl} S 4-nitro- (4-nitro-piperazin-1-yl {[(4-nitrophenyl)- B46 phenyl phenyl)- [(4-nitrophenyl)-sulfonyl sulfonyl]- amino]carbothioyl}

Compound data and systematic names for the compounds in Table 3 are asfollows:

-   B45 (C₁₈H₁₈N₆O₄S₂; MW=446.506):-   N¹,N⁴-bis (4-nitrophenyl)-1,4-piperazinedicarbothioamide;-   B46 (C₃₀H₂₄N₈O₁₂S₄; MW=816.822):-   4-nitro-N-{[4-({4-nitro[(4-nitrophenyl)sulfonyl]anilino}-carbothioyl)-1-piperazinyl]carbothioyl}-N-(4-nitrophenyl)benzenesulfonamide.

The present invention is further illustrated by the followingnon-limiting experimental part.

Preparation of the Compounds of the Present Invention

All compounds having the general formula (III) were prepared inbasically the same manner, viz by reacting a suitable isocyanate orisothiocyanate derivative with a suitable amine or amide derivative.This is illustrated by the preparation of B51, B48, B49, B641 and B674as set forth hereinbelow.

Preparation of B51:

-   -   In a round bottomed flask, 4-cyanoaniline (0.01 mol) was        dissolved in acetone (40 ml), followed by addition of an aqueous        10% KOH solution (5.6 g) and 4-nitrophenylisothiocyanate (1.8 g,        0.01 mol). The reaction mixture was refluxed for 4 h, after        which the solvent was evaporated. Distilled water was then        added, and the pH was adjusted to 7 by using aqueous 2N (or 20%)        HCl, thus yielding a product precipitate, which was filtered off        and dried in an oven at 40° C. Compound B51 was obtained in 66%        yield as an orange powder.

Preparation of B48:

-   -   In a round bottomed flask, tetrahydrofurfurylamine (1.01 g, 0.01        mol, ρ=0.98) was mixed with acetone (40 ml), aqueous 10% KOH        solution (5.6 g) and phenylisothiocyanate (1.36 g, 0.01 mol,        p=1.13), after which the reaction mixture was refluxed until the        reaction was completed. Then the solvent was evaporated, water        added and the pH adjusted to 7 by using aqueous 2N HCl, thus        yielding a product precipitate, which was filtered off and dried        in an oven at 40° C. Compound B48 was obtained in 86% yield as        an off-white powder.

Preparation of B49:

-   -   Phenylisothiocyanate (1.36 g, 0.01 mol) was reacted with        4-amino-3,5-diiodobenzoic acid (3.88 g, 0.01 mol) as described        for B51, thus yielding B49 in 75% yield as a pale yellow powder.

Preparation of B641:

-   -   4-nitrophenylisocyanate (3.28 g, 0.02 mol) was reacted with        1,5-pentanediamine (1.02 g, 0.01 mol) as described for B51, thus        giving B641 in 60% yield as a yellow powder.

Preparation of B674:

-   -   4-fluorobenzeneisothiocyanate (1.53 g, 0.01 mol) was reacted        with N-(1-(2,6-diclorophenyl)-2-oxoethyl)-guanidine (2.46 g,        0.01 mol) as described for B48, thus giving B674 in 65% yield as        a yellow powder.

The preparation of compounds having the general formula (IV) is normallyperformed in two reaction steps. Firstly, a suitable isocyanate orisothiocyanate derivative (1 eq.) is reacted with a suitable amine oramide derivative (1 eq.), whereby a disubstituted (thio)urea derivativeis formed. Secondly, the disubstituted (thio)urea derivative is reactedwith a suitable electrophile (2 eq.), whereby the desiredtetrasubstituted (thio)urea derivative having the general formula (IV)is obtained. Typically, the preparation of compounds having the generalformula (Iv) is performed in basically the same manner as in thefollowing examples.

Preparation of B35-4:

-   -   4-nitrophenylisocyanate (1.8 g, 0.01 mol) and        2-amino-6-nitrobenzothiazole (4.57 g, 0.01 mol) were reacted as        described for B51. The resulting intermediate product was then        dissolved in N,N-dimethylformamide (DMF; 40 ml) and reacted with        2,5-dibromopyridine (4.73 g, 0.02 mol) in the presence of        pyridine (2 ml). The reaction mixture was refluxed for 6 h,        after which the DMF was evaporated and the residue was dissolved        in 99% ethanol, after which the pH of the resulting solution was        adjusted to 7 with aqueous 20% NaOH, whereby the product was        precipitated. The precipitate was filtered off, washed with        ethanol and dried in an oven at 40° C., thus giving B35-4 as a        yellow powder in 55% yield.

Preparation of B42-37:

-   -   4-fluorobenzeneisothiocyanate (1.37 g, 0.01 mol) and        4-methylbenzenesulfonamide (1.87 g, 0.01 mol) were reacted as        described for B51. The resulting intermediate product was then        dissolved in DMF (70 ml) and reacted with        4-nitrobenzenesulfonylchloride (4.43 g, 0.02 mol) in the        presence of pyridine (0.02 mol). The reaction mixture was        refluxed for 6 h, and after work-up as described for B35-4, the        product B42-37 was obtained as an orange powder in 63% yield.

Alternatively, a compound having the general formula (IV) may beprepared by derivatizing a commersially available disubstituted urea orthiourea derivative, e.g. Gliclazide, Glipizide, Gliquidone, Glisoxepidor Gluborid, with a suitable electrophile. Some examples of suchderivatizations are the compounds B801 and B803-B808.

Compounds having the general formula (V) are typically prepared byreacting a suitable isocyanate or isothiocyanate derivative (1-2 eq.)with a suitable nitrogen containing cyclic compound (1 eq.) having atleast one amine functionality. The obtained product (1 eq.) is thenoptionally treated with a suitable electrophile (2 eq.). The preparationof B45 and B46 illustrates the synthesis of this type of compounds. Italso deserves to be mentioned that compounds having the general formula(V) are often symmetrical, i.e. have at least one element of symmetry.

Preparation of B45:

-   -   4-nitrophenylisothiocyanate (3.60 g, 0.02 mol) and piperazine        (0.86 g, 0.01 mol) were reacted as described for B48 supra,        thereby giving B45 as a red powder in 32% yield.

Preparation of B46:

-   -   B45 (4.47 g, 0.01 mol) was reacted with        4-nitro-benzenesulfonylchloride (4.43 g, 0.02 mol) as described        for B35-4, thereby giving B46 as a white powder in 46% yield.

As an illustration, the structure of B46 is given hereinbelow:

As non-limiting examples of the present invention, typical suitableisocyanate or isothiocyanate derivatives used are butylisocyanate,4-nitrophenylisothiocyanate, 4-nitrophenylisocyanate,4-fluorophenylisothiocyanate, 4-fluorophenylisocyanate,phenylisothiocyanate, 3,5-diiodo-4-isothiocyanatobenzoic acid,cyclohexylisocyanate, 8-chloro-5-isothiocyanatoquinoline,1,2-diiodo-3-isothiocyanatopropane, 3-chloro-4-isothiocyanatopyridine,4-trifluoromethylbenzeneisothiocyanate and2-hydroxy-4-isothiocyanatobenzoic acid.

As non-limiting examples of the present invention, typical suitableamine and amide derivatives used are 4-methylbenzenesulfonamide,5-indanesulfonamide, 5-(dimethylamino)-1-naphthalenesulfonamhide,1,1-dioxo-1,2,3,4-tetrahydro-1λ⁶-thiochromene-7-sulfonamide,7-fluoro-2,1,3-benzoxadiazole-4-sulfonamide, 3-chloro-4-pyridinamine,2-amino-6-nitrobenzothiazole, 2-amino-4-nitrobenzothiazole,S-aminoisophthalic acid, 2-amino-5-nitrothiazole,3,4,5-trimethoxyaniline, 2-chloro-4-pyrimidinamine, 4-isopropylaniline,2-amino-4-methyl-thiazole, tetrahydrofurfurylamine,4-amino-3,5-diiodo-benzoic acid, glycine, 2,3-diiodo-1-propanamine,4-aminobenzonitrile, 4-(2-aminoethyl)morpholine,4-(aminomethyl)pyridine, 2-amino-5-[(4-nitrophenyl)sulphon-yl]thiazole,(2S,5R)-6-amino-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylicacid, 1-aminocyclopentanecarboxylic acid,4-(aminomethyl)cyclohexanecarboxylic acid, 4-aminocyclo-hexanecarboxylicacid, 3-aminobenzoic acid, 2-trifluoromethyl-4-nitroaniline,2-nitro-4-trifluoromethylaniline, 3-trifluoromethyl-4-chloroaniline,2,3,6-trifluoro-5-aminobenzoic acid,3,4,5-trifluorophenyl-2,5-dicyanoaniline,3-chloro-2,5,6-trifluoro-4-pyridinamine, 2,2,2-trifluoroethylamine,4-trifluoromethylaniline, 8-chloro-5-quinolinamine,(2-amino-5-iodophenyl)(phenyl)methanone,2-amino-3-(4-iodophenyl)naphthaquinone, 4-iodophenylalanine,4-amino-1-[3,4-dihydroxy-5-(hydroxy-methyl)tetrahydro-2-furanyl]-5-iodo-2(1H)-pyrimidone,4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenylalanine,4-hydroxy-3-iodophenylalanine, 2-iodo-2-aminobenzoic acid,2-(6-amino-9H-purin-9-yl)-5-(iodomethyl)tetrahydro-3,4-furandiol,4-amino-3,5,6-trichloro-2-pyridinecarboxylic acid,3-amino-2-quinoxalinecarboxylic acid, 4-amino-2-quinolinecarboxylicacid, 4-amino-5-pyrimidinecarboxylic acid,3-aminobi-cyclo[2.2.1]heptane-2-carboxylic acid,2-amino-6-hydroxy-4-pyrimidinecarboxylic acid,2-amino-5-chloro-4-pyrimidinecarboxylic acid,1-amino-9,10-dioxo-9,10-dihydro-2-anthracenecarboxylic acid,3-amino-1-adamantanecarboxylic acid,(1S,3R)-1-amino-1,3-cyclopentanedicarboxylic acid,2-(ethylsulfanyl)-5-pyrimidinecarboxylic acid,3-amino-1,1,3-propanetricarboxylic acid, 3-amino-2-pyrazinecarboxylicacid, 1-aminocyclopropanecarboxylic acid,2-(1-(1-amino-2-oxoethyl)-2,3,4-trihydroxybutoxy)propanoic acid,2-amino-6-((1S,2R)-1,2,3-trihydroxypropyl)-4(8H)-pteridone,5-(2-aminoethyl)-1,2,4-benzenetriol,5-amino-2,6-dioxo-1,2,3,6-tetrahydro-4-pyrimidinecarboxylic acid,4-amino-1,3-dihydroxy-9,10-dioxo-8a,9,10,10a-tetrahydro-2-anthracenesulfonicacid, 2,4,5-trihydroxyphenylalanine,6-amino-3-(3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl)-4(3H)-pyrimidone,4-((1S,1R)-2-amino-1-hydroxypropyl)-1,2-benzenediol,4-(aminomethyl)-1,2-benzenediol,4-amino-1-(3,4-dihydroxy-5-(hydroxymethyl)-tetrahydro-2-furanyl)-5-methyl-2(1H)-pyrimidone,4-amino-1-(3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl)-2(1H)-pyrimidinethione,4-amino-1-(3,4-dihydroxy-5-(hydroxymethyl) tetrahydro-2-furanyl)-2(1R)-pyrimidone, 3,6-diamino-1,8-dihydroxy-dihydro-anthra-9,10-quinone,4-(2-aminoethyl)-1,2-benzenediol,4-(2-amino-1-hydroxyethyl)-1,2-benzenediol,1-amino-1,3-cyclobutanedicarboxylic acid,(1R,3R)-1-amino-1,3-cyclopentanedicarboxylic acid,2-(2-aminobenzoyl)benzoic acid, 6-aminonicotinic acid,1-aminocyclohexanecarboxylic acid,2-aminobicyclo[2.2.1]-heptane-2-carboxylic acid, 1,2-ethanediamine,1,4-butanediamine, 1,4-benzenediamine, 1,5-pentanediamine,4′-amino(1,1′-biphenyl)-4-ylamine, 2-amino-4,5-dihydroxy-pyrazine,2-amino-4,5-pyrimidinediol, 4′-amino-3,3′-dichloro(1μl-biphenyl)-4-ylamine, 4′-amino-3,3′-dimethyl(1,1′-biphenyl)-4-ylamine,N¹,N¹-diethyl-1,4-pentanediamine, 3,4-acridinediamine,3,6-acridinediamine,2,4-dibromo-6-([cyclohexyl(methyl)amino]methyl)aniline,4-N,N-dimethylaminoaniline, 2-amino-6-chloropyrazine,2-amino-6-chloropyridine, 2-amino-5-chloropyridine,2-((Z)-(2,6-dichlorophenyl) methylidene)-1-hydrazinecarboximidamide,2-{[amino(imino)methyl]amino}acetic acid,N-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)guanidine,N-(3-methyl-2-butenyl)guanidine,N-(1,4-dioxaspiro(4.5)dec-2-ylmethyl)guanidine,N-(1-(2,6-dichlorphenyl)-2-oxoethyl)guanidine, N-cyanoguanidine,guanidine,N-(3-{[amino(imino)methyl]amino}-2,4,5,6-tetrahydroxycyclohexyl)guanidineand2-{(E)-3-(5-nitro-2-furyl)-1-((E)-2-(5-nitro-2-furyl)ethenyl)-2-propenylidene}-1-hydrazinecarboximidamide.

As non-limiting examples of the present invention, suitableelectrophiles used are 2,5-dibromopyridine, 2,6-dibromopyridine,2,3-dichloropyridine, 2,5-dichloropyrazine, 2,6-dichloropyrazine,2-chloropyrazine, 2,6-dichloropyridine, 4-nitrobenzenesulfonylchloride,4-fluorobenzenesulfonylchloride, benzenesulfonylchloride,trifluoromethylsulfonylchloride, 2-naphthalenesulfonylchloride andethanesulfonylchloride.

By guidance of the examples above and known literature, e.g. U.S. Pat.No. 5,776,982, EP 0 015 110 and U.S. Pat. No. 4,486,439 as well asreferences cited therein, it is realized by a person skilled in the artthat the preparation of the compounds according to the present inventionis readily accomplished.

Biological Evaluation of the Present Compounds

The antiparasitic activity of the present compounds as prophylacticagents was evaluated in vivo on 100 one day old (1 day after hatch)chickens of Habbared X breed. The chickens were divided into five groupsof 20 birds each, and each group was located in a separate pen (1 m×1m). The chickens were then fed with unmedicated food up to day 7 afterhatch. Fresh water was supplied ad libitum.

On day 8 after hatch, the five groups were given feed containing thefollowing compounds (1 ppm=1 mg drug/kg feed):

-   -   Group #1: B49 (100 ppm);    -   Group #2: B42 (150 ppm);    -   Group #3: B46 (100 ppm);    -   Group #4: Coxistac (60 ppm), a known anticoccidial agent (see        U.S. Pat. No. 3,857,948);    -   Group #5: no drug content (control group).

The chickens were fed as above on day 8 and 9 after hatch. On day 10after hatch, each chicken was infected orally by 6 000-7 000 oocystscontaining a mixture of 5 mature sporulated strains, namely E.acervulina, E. maxima, E. necatrix, E. tenella and E. brunetti. Thegroups #1-4 received drug as above from day 10 to 21 after hatch.

From day 14 to 21 after hatch, fresh fecal droplets were collected andexamined daily. The average number of oocysts/g faeces was thencalculated in accordance with the co-called Mc-Master technique(Soulsby, 1984). The final weight and mean total amount of consumed feedof each bird were also examined, and the results are summarized in Table1 hereinbelow.

TABLE 1 Anticoccidial effect of B42, B46 and B49 on chicken of HabbaredX breed Average number of Eimeria spp. oocysts/g faeces Mean amountGroup Day after hatch Mean body of feed (drug) 14 15 16 17 18 19 21Total weight (g) consumed (g) #1 0.0 3000 10000 20000 0.0 0.0 0.0 3300066.0 95 (B49) #2 0.0 0.0 3000  7000 0.0 0.0 0.0 10000 61.0 93 (B42) #30.0 3000 14000 99000 6000 0.0 0.0 122000  54.5 39.3 (B46) #4 0.0 30004000  7000 2000 2000 0.0 18000 62.0 120 (Coxistac) #5 0.0 15000 240001.3 × 10⁶ 174000 0.0 0.0 1.4 × 10⁶ 57.3 120 (no drug)

As can be seen from the total number of oocysts/g faeces in Table 1, thecompounds B49 and B42 have an anticoccidial effect similar to that ofCoxistac. But more importantly, the duration of the anticoccidialinfection was also shorter in the chickens treated with B49 and B42 ascompared to Coxistac. This was in turn manifested in the −20% loweramount of feed consumed in the groups treated with B49 and B42 ascompared to both the Coxistac and the non-treated group. In any largescale breeding plant or operation, the properties of B49 and B42 shouldtherefore be highly advantageous, since use thereof both reduces feedingcosts and the amount of faeces without any loss of growth rate.

According to Table 1, the anticoccidial effect of B46 may at first seeminferior to that of Coxistac due to its comparatively higher totalnumber of oocysts/g faeces. However, this is not the case, since the netresult of using feed containing B46 is a fair body weight gain incombination with a surprisingly low feed intake. In fact, the feedconsumption was ˜67% lower in the B46 treated group in comparison withthe Coxistac treated group. Since the body weight gain is stillacceptable, this reduced feed consumption provides a considerableadvantage in any large scale breeding plant or operation.

Moreover, the prophylactic anticoccidial effect of B42, B49 and B51 wasalso evaluated in chickens of Arbor Aker breed. These trials wereconducted by using basically the same test protocol as that used for thechickens of Habbared X breed, albeit with the following modifications:

-   -   i) On day 3 after hatch, the tested groups of chickens receieved        feed containing 100 ppm of B42, B49, B51 or Coxistac (60 ppm);    -   ii) On day 7 after hatch, the chickens were infected orally by        oocysts containing a mixture of 8 mature sporulated strains,        namely E. mitis, E. hagani, E. praecox, E. acervulina, E.        maxima, E. necatrix, E. tenella and E. brunetti.

For B42 and B49, the results were essentially the same as those reportedfor the trials with the chickens of Habbared X breed (vide supra),whereas the results for B51 were comparable with those of B42.

In summary, it should be clear from this disclosure that the compoundsaccording to the present invention are versatile new agents forantiparasitic treatment. Indeed, they are particularly suitable fortreatment of coccidiosis and disorders related thereto, especially inpoultry.

1. A compound having the general formula (I):

wherein Y is selected from O and S; R₁ is selected from the groupconsisting of 4-chloro-3-trifluoromethyl phenyl,N-hexahydrocyclopental[c]pyrrol-2(1H)-yl, 4-methylphenyl, 5-isophthalyl,6-nitro-1,3-benzothiazol-2-yl, 4-(morpholino)ethyl, 4-cyanophenylN-3-chloro-2,5,6-trifluoro-4-pyridinyl,3-chloro-2,5,6-trifluoro-4-pyridinyl, 2,4,5-trihydroxyphenethyl,3-carboxylphenyl, -3-(1adamantanecarboxylic acid),2,3-dihydro-1H-inden-5-sulfonyl, 4-chlorophenyl, 3,4,5-trimethoxyphenyl,tetrahydro-2-furanylmethyl, 5-chloro-2-pyridinyl, 5-chloro-2-pyrazinyl,4-carboxy-3-hydroxy-phenyl, 6-chloro-2-pyrazinyl, 4-fluorophenyl and1-carboxy-cyclopentyl; R₂ is selected from the group consisting of(4-fluorophenyl)sulfonyl, (4-nitrophenyl)sulfonyl, 2,2,2-trifluoroethyl,2-naphtylsulfonyl, 5-bromo-2-pyridinyl, 6-chloro-2-pyrazinyl, andphenyl-sulfonyl; R₃ is selected from the group consisting of(4-fluorophenyl)sulfonyl, (4-nitrophenyl)sulfonyl, 6-chloro-2-pyrazinyl,2-naphtylsulfonyl, 5-bromo-2-pyridinyl, 4-cyanophenyl, andphenyl-sulfonyl; and R₄ is selected from the group consisting of4-nitrophenyl, (4-nitrophenyl)sulfonyl, 4-fluorophenyl, 4-phthalyl,8-chloro-5-quinolinyl, cyclohexyl, methyl-4-cyclohexancarboxylic acid,phenyl, 3,5-diiodo-4-carboxyphenyl.
 2. A compound according to claim 1wherein R₂ is equal to R₃.
 3. A compound according to claim 1, whereinNR₁R₂ and NR₃R₄ are not identical.
 4. A pharmaceutical compositioncomprising a compound according to claim 1 as active ingredient inassociation with a pharmaceutically acceptable adjuvant, diluent orcarrier.
 5. A pharmaceutical composition comprising a compound accordingto claim 2 as active ingredient in association with a pharmaceuticallyacceptable adjuvant, diluent or carrier.
 6. A pharmaceutical compositioncomprising a compound according to claim 3 as active ingredient inassociation with a pharmaceutically acceptable adjuvant, diluent orcarrier.
 7. An animal feed, feed concentrate or drinking watercomprising a compound according to claim
 1. 8. An animal feed, feedconcentrate or drinking water comprising a compound according to claim2.
 9. An animal feed, feed concentrate or drinking water comprising acompound according to claim
 3. 10. A method for treatment ofcoccidiosis, wherein said method comprises administering to an animal ofa therapeutically effective amount of a compound according to claim 1.11. A method for treatment of coccidiosis, wherein said method comprisesadministering to an animal of a therapeutically effective amount of acompound according to claim
 2. 12. A method for treatment ofcoccidiosis, wherein said method comprises administering to an animal ofa therapeutically effective amount of a compound according to claim 3.